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Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters. [ABSTRACT FROM AUTHOR]

Purpose: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model.Methods: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data.Results: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation.Conclusions: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model. [ABSTRACT FROM AUTHOR]

Background: This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.Methods: This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS).Results: Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011).Conclusions: LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment. [ABSTRACT FROM AUTHOR]

Dysphagia represents one of the most serious adverse events after curative-intent treatments with a tremendous impact on quality of life in patients with head and neck cancers. Novel surgical and radiation therapy techniques have been developed to better preserve swallowing function, while not negatively influencing local control and/or overall survival. This review focuses on the current literature of swallowing outcomes after curative treatment strategies. Available results from recent studies relevant to this topic are presented, demonstrating the potential role of new treatment modalities for early- and intermediate-stage oropharyngeal cancers. Based on this, we present the rationale and design of the currently active EORTC 1420 "Best of" trial, and highlight the potential of this study to help prioritizing either surgery- or radiation-based treatment modalities for the treatment of oropharyngeal cancer in the future. [ABSTRACT FROM AUTHOR]

Background: The last few years, in radiotherapy there has been a growing focus on speed of treatment delivery (largely driven by economical and commercial interests). This study investigates the influence of treatment time on plan quality for helical tomotherapy (HT), using delivery times with Volumetric Modulated Arc Therapy (VMAT; Rapid Arc [RA]) as reference.Methods: In a previous study, double arc RA (Eclipse) and standard HT plans (TomoHD™) were created for five oropharyngeal cancer patients and reported according to ICRU 83 guidelines. By modifying the beam width from 2.5 to 5.0 cm, elevating the pitch and lowering the modulation factor, "TomoFast" (TF) plans were generated with treatment times equal to RA plans. To quantify the impact of TF's craniocaudal gradient, similar plans were generated on TomoEdge(TM) (TomoEdgeFast;TEF). The homogeneity index (HI), conformity index (CI), mean dose, Dnear-max (D2) and Dnear-min (D98) of the PTVs were analyzed as well as the mean dose, specific critical doses and volumes of 26 organs at risk (OARs). Data were analyzed using repeated measures ANOVA.Results: With a mean treatment time of 3.05 min (RA), 2.89 min (TF) and 2.95 min (TEF), PTVtherapeutic coverage was more homogeneous with TF (HI.07;SE.01) and TEF (HI.08;SE.01) compared to RA (HI.10;SE.01), while PTVprophylactic was most homogeneous with RA. Mean doses to parotid glands were comparable for RA, TF, TEF: 25.62, 25.34, 23.09 Gy for contralateral and 32.02, 31.96, 30.01 Gy for ipsilateral glands, respectively. OARs' mean doses varied between different approaches not favoring a particular technique. TF's higher dose to OARs at the cranial-caudal edges of the PTVs and its higher integral dose, both due to the extended cranial-caudal gradient, seems to be solved by the new TomoEdge™ software. However, all these faster techniques lose part of standard TomoHD's OAR sparing capacityConclusion: It is possible to treat oropharyngeal cancer patients using HT (TF/TEF) within time-frames observed for RA maintaining comparable target coverage and sparing of OARs. This study indicates that treatment time is not technology specific, rather an operator's decision on balancing efficiency and quality. [ABSTRACT FROM AUTHOR]

• Our GORTEC internationally-reviewed consensus showed that the flap-tissue junction should be considered at higher risk of tumor spread compared to other areas of the flap. • Surgeons should report the placement of flaps more accurately and consider clip placement to guide radiotherapy planning. • The risks of radiation-induced atrophy, fibrosis, and osteoradionecrosis should be considered during radiotherapy optimization. Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns. [ABSTRACT FROM AUTHOR]

The authors reflect on the oropharyngeal carcinoma related to human papillomavirus (HPV). The author is critical on sexual transmission of HPV which might be the reason for the increase in incidence of HPV related oropharyngeal carcinoma through orogenital intercourse and its implications for health service providers and commissioners. They suggest that clinicians should not change the treatment policies and aim to offer the opportunity to enroll in an appropriate clinical trial.

• In total, more than 4000 adult patients are currently treated with PT across Europe annually. • CNS and HNC tumours are the most frequently treated tumour sites. • Most centres use national or institutional guidelines for selecting patients for PT. • Treatments are usually reimbursed by national health care systems. • Most patients are included in prospective data registries and clinical trials. Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT. [ABSTRACT FROM AUTHOR]

Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit. [ABSTRACT FROM AUTHOR]

• The two most commonly used hypoxia PET tracers FMISO and FAZA can be analyzed jointly. • Hypoxia PET derived parameters delivered strong and independent prognostic value. • Hypoxia specific treatment did not improve outcome in exploratory post hoc analyses. Tumor hypoxia plays an important role in head and neck squamous cell carcinomas (HNSCC). Various positron emission tomography (PET) tracers promise non-invasive assessment of tumor hypoxia. So far, the applicability of hypoxia PET is hampered by monocentric imaging trials with few patients. Multicenter individual patient data based meta-analysis of the original PET data from four prospective imaging trials was performed. All patients had localized disease and were treated with curatively intended radio(-chemo)therapy. Hypoxia PET imaging was performed with 18F-Fluoromisonidazole (FMISO, 102 patients) or 18F-Fluoroazomycin-arabinoside (FAZA, 51 patients). Impact of hypoxia PET parameters on loco-regional control (LRC) and overall survival (OS) was analyzed by uni- and multivariable Cox regression. Baseline characteristics between participating centers differed significantly, especially regarding T stage (p < 0.001), tumor volume (p < 0.001) and p16 status (p = 0.009). The commonly used hypoxia parameters, maximal tumor-to-muscle ratio (TMR max) and hypoxic volume with 1.6 threshold (HV 1.6), showed a strong association with LRC (p = 0.001) and OS (p < 0.001). These findings were irrespective of the radiotracer and the same cut-off values could be applied for FMISO and FAZA (TMR max > 2.0 or HV 1.6 > 1.5 ml). The effect size of TMR max was similar for subgroups of patients defined by radiotracer, p16 status and FDG-PET parameters for LRC and OS, respectively. PET measured hypoxia is robust and has a strong impact on LRC and OS in HNSCC. The most commonly investigated tracers FMISO and FAZA can probably be used equivalently in multicenter trials. Optimal strategies to improve the dismal outcome of hypoxic tumors remain elusive. [ABSTRACT FROM AUTHOR]

Purpose: Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff.Methods and Materials: A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases.Results: In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care.Conclusions: This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) consensus contouring guidelines in the postoperative setting for complex cutaneous squamous cell carcinoma of the head and neck have been developed by expert clinicians in the field of head and neck and dermato-oncology and members of the Head and Neck Cancer International Group to assist radiation oncologists involved in the management of this disease. These guidelines present a set of principles used to define postoperative RT volumes and corresponding minimum doses after resection of all macroscopic tumor with or without microscopic residual disease. It is anticipated they will promote the harmonization of postoperative RT globally and contribute to a reduction in treatment variation among clinicians, allowing for RT quality and outcomes assessment across institutions. [ABSTRACT FROM AUTHOR]

Purpose: To propose an automatic atlas-based segmentation framework of the dental structures, called Dentalmaps, and to assess its accuracy and relevance to guide dental care in the context of intensity-modulated radiotherapy. Methods and Materials: A multi-atlas–based segmentation, less sensitive to artifacts than previously published head-and-neck segmentation methods, was used. The manual segmentations of a 21-patient database were first deformed onto the query using nonlinear registrations with the training images and then fused to estimate the consensus segmentation of the query. Results: The framework was evaluated with a leave-one-out protocol. The maximum doses estimated using manual contours were considered as ground truth and compared with the maximum doses estimated using automatic contours. The dose estimation error was within 2-Gy accuracy in 75% of cases (with a median of 0.9 Gy), whereas it was within 2-Gy accuracy in 30% of cases only with the visual estimation method without any contour, which is the routine practice procedure. Conclusions: Dose estimates using this framework were more accurate than visual estimates without dental contour. Dentalmaps represents a useful documentation and communication tool between radiation oncologists and dentists in routine practice. Prospective multicenter assessment is underway on patients extrinsic to the database. [ABSTRACT FROM AUTHOR]