Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

BACKGROUND: Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. METHODS: This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. RESULTS AND CONCLUSION: Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Comparison of conventional and hippocampus-sparing radiotherapy in nasopharyngeal carcinoma: In silico study and systematic review.

Background and purpose: Radiation-induced damage to the hippocampi can cause cognitive decline. International recommendations for nasopharyngeal cancer (NPC) radiotherapy (RT) lack specific guidelines for protecting the hippocampi. Our study evaluates if hippocampi-sparing (HS) RT in NPC ensures target coverage and meets recommended dose limits for other at-risk organs. Materials and methods: In a systematic literature review, we compared hippocampal D40% in conventional and HS RT plans. In an in silico dosimetric study, conventional and HS-VMAT plans were created for each patient, following international recommendations for OAR delineation, dose prioritization and acceptance criteria. We assessed the impact on neurocognitive function using a previously published normal tissue complication probability (NTCP) model. Results: In four previous studies (n = 79), researchers reduced D40% hippocampal radiation doses in HS plans compared to conventional RT on average from 24.9 Gy to 12.6 Gy.Among 12 NPC patients included in this in silico study, statistically significant differences between HS and conventional VMAT plans were observed in hippocampal EQD2 Dmax (23.8 vs. 46.4 Gy), Dmin (3.8 vs. 4.6 Gy), Dmean (8.1 vs. 15.1 Gy), and D40% (8.3 vs. 15.8 Gy). PTV coverage and OAR doses were similar, with less homogeneous PTV coverage in HS plans (p = 0.038). This translated to a lower probability of memory decline in HS plans (interquartile range 15.8-29.6 %) compared to conventional plans (33.8-81.1 %) based on the NTCP model (p = 0.002). Conclusion: Sparing the hippocampus in NPC RT is safe and feasible. Given the life expectancy of many NPC patients, their cognitive well-being must be paramount in radiotherapy planning.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

BACKGROUND: Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial. METHODS: Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset. RESULTS: Cluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site. CONCLUSIONS: These data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection. TRIAL REGISTRATION NUMBER: EudraCT Number: 2017-000562-30.

vOARiability: Interobserver and intermodality variability analysis in OAR contouring from head and neck CT and MR images.

BACKGROUND: Accurate and consistent contouring of organs-at-risk (OARs) from medical images is a key step of radiotherapy (RT) cancer treatment planning. Most contouring approaches rely on computed tomography (CT) images, but the integration of complementary magnetic resonance (MR) modality is highly recommended, especially from the perspective of OAR contouring, synthetic CT and MR image generation for MR-only RT, and MR-guided RT. Although MR has been recognized as valuable for contouring OARs in the head and neck (HaN) region, the accuracy and consistency of the resulting contours have not been yet objectively evaluated. PURPOSE: To analyze the interobserver and intermodality variability in contouring OARs in the HaN region, performed by observers with different level of experience from CT and MR images of the same patients. METHODS: In the final cohort of 27 CT and MR images of the same patients, contours of up to 31 OARs were obtained by a radiation oncology resident (junior observer, JO) and a board-certified radiation oncologist (senior observer, SO). The resulting contours were then evaluated in terms of interobserver variability, characterized as the agreement among different observers (JO and SO) when contouring OARs in a selected modality (CT or MR), and intermodality variability, characterized as the agreement among different modalities (CT and MR) when OARs were contoured by a selected observer (JO or SO), both by the Dice coefficient (DC) and 95-percentile Hausdorff distance (HD 95 $_{95}$ ). RESULTS: The mean (±standard deviation) interobserver variability was 69.0 ± 20.2% and 5.1 ± 4.1 mm, while the mean intermodality variability was 61.6 ± 19.0% and 6.1 ± 4.3 mm in terms of DC and HD 95 $_{95}$ , respectively, across all OARs. Statistically significant differences were only found for specific OARs. The performed MR to CT image registration resulted in a mean target registration error of 1.7 ± 0.5 mm, which was considered as valid for the analysis of intermodality variability. CONCLUSIONS: The contouring variability was, in general, similar for both image modalities, and experience did not considerably affect the contouring performance. However, the results indicate that an OAR is difficult to contour regardless of whether it is contoured in the CT or MR image, and that observer experience may be an important factor for OARs that are deemed difficult to contour. Several of the differences in the resulting variability can be also attributed to adherence to guidelines, especially for OARs with poor visibility or without distinctive boundaries in either CT or MR images. Although considerable contouring differences were observed for specific OARs, it can be concluded that almost all OARs can be contoured with a similar degree of variability in either the CT or MR modality, which works in favor of MR images from the perspective of MR-only and MR-guided RT.

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial.

BACKGROUND: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue. PATIENTS AND METHODS: Ten oropharyngeal cancer patients with post-radiation xerostomia and no evidence of disease recurrence 2 or more years after (chemo)irradiation (intervention group) and 10 healthy volunteers (control group) will be enrolled in this nonrandomized, open-label, phase I exploratory study. MSCs from umbilical cord tissue will be inserted under ultrasound guidance into both parotid glands and both submandibular glands of the patients. Toxicity of the procedure will be assessed according to CTCAE v5.0 criteria at days 0, 1, 5, 28, and 120. Efficacy will be assessed by measuring salivary flow and analyzing its composition, scintigraphic evaluation of MSC grafting, retention, and migration, and questionnaires measuring subjective xerostomia and quality of life. In addition, the radiological, functional, and morphological characteristics of the salivary tissue will be assessed before, at 4 weeks, and at 4 months after the procedure. In the control group subjects, only salivary flow rate and salivary composition will be determined. DISCUSSION: The use of allogeneic MSCs from umbilical cord tissue represents an innovative approach for the treatment of xerostomia after radiation. Due to the noninvasive collection procedure, flexibility of cryobanking, and biological advantages, xerostomia therapy using allogeneic MSCs from umbilical cord tissue may have an advantage over other similar therapies.

Review of Outcomes after Salvage Surgery for Recurrent Squamous Cell Carcinoma of the Head and Neck.

Surgery with adjuvant chemoradiotherapy or chemoradiotherapy is the mainstay in treatment for advanced stage head and neck squamous cell carcinoma; however, locoregional recurrences are frequent. Salvage surgery could be proposed in selected patients to improve local control, disease-free, and overall survival. Factors for improved disease-free and overall survival in patients treated with salvage surgery include age, tumor location, the initial T stage, HPV status, resection margins, and the time elapsing from the initial treatment. Clinical trials with adjuvant therapies have shown promise after salvage surgery in terms of tolerance and response, but clinical guidelines for using these adjuvant treatments are currently lacking. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.

Progress and emerging strategies to preserve function in the treatment of sinonasal cancer.

The sinonasal structures and their adjacent organs host several functions including vision, olfaction, nasal respiration and filtration, secretory immunity, facial expression, articulation, and oral deglutition. We reviewed the current evidence supporting functional preservation in sinonasal cancer treatment. Primary surgery with or without adjuvant modalities continues to be the standard of care for sinonasal cancer. Unfortunately, functional compromise remains a dominant negative feature of this approach. More recently, through advances in therapeutic techniques and improved understanding of the relevant tumor biology, treatments aimed at preserving function and cosmesis are emerging. The evidence for such progress involving minimal access surgery, surgical reconstruction for rehabilitation, new techniques in radiation therapy, inclusion of systemic and locally enhanced chemotherapy, and therapeutic agents based on molecular targets are highlighted. This multi-prong approach bodes well for future patients with sinonasal cancer to undergo successful treatment that includes maximal preservation of associated functions.

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis.

BACKGROUND: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. OBJECTIVE: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. METHODS: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. RESULTS: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. CONCLUSIONS AND SIGNIFICANCE: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment.

The QuADRANT study: Current status and recommendations for improving uptake and implementation of clinical audit of medical radiological procedures in Europe. The radiotherapy perspective.

BACKGROUND: QuADRANT was a research project funded by the European Commission to evaluate clinical audit uptake and implementation across Europe, with an emphasis on clinical audit as mandated within the BSSD (Basic Safety Standards Directive). AIM: Focusing on the QuADRANT objectives - to obtain an overview of European clinical audit activity; identify good practices, resources, barriers and challenges; provide guidance and recommendations going forwards; identify the potential for European Union action on quality and safety focusing on the field of radiotherapy. RESULTS: A pan-European survey, expert interviews and a literature review conducted within the framework of the QuADRANT project indicated that developments in national clinical audit infrastructure are required. While in radiotherapy, there is a strong tradition and high level of experience of dosimetry audits and well-established practice through the IAEA's QUATRO audits, few countries have a well-established comprehensive clinical audit programme or international/national initiatives on tumour specific clinical audits. Even if sparse, the experience from countries with established system of quality audits can be used as role-models for national professional societies to promote clinical audit implementation. However, resource allocation and national prioritisation of clinical audit are needed in many countries. National and international societies should take the initiative to promote and facilitate training and resources (guidelines, experts, courses) for clinical audits. Enablers used to enhance clinical audit participation are not widely employed. Development of hospital accreditation programmes can facilitate clinical audit uptake. An active and formalised role for patients in clinical audit practice and policy development is recommended. Because there is a persisting variation in European awareness of BSSD clinical audit requirements, work is needed to improve dissemination of information on the legislative requirements relating to clinical audit in the BSSD and in relation to inspection processes. The aim is to ensure these include clinical audit and that they encompass all clinics and specialties involved in medical applications using ionising radiation. CONCLUSION: QuADRANT provided an overarching view of clinical audit practice in Europe, with all its related aspects. Unfortunately, it showed that the awareness of the BSSD requirements for clinical audit are highly variable. Therefore, there is an urgent need to dedicate efforts towards ensuring that regulatory inspections also incorporate an assessment of clinical audit program(s), affecting all aspects of clinical work and specialties involved in patient exposure to ionising radiation.

The Incidence and the Risk Factors for Pharyngocutaneous Fistula following Primary and Salvage Total Laryngectomy.

The pharyngocutaneous fistula (PCF) is the most common complication following a total laryngectomy (TL) with a wide range of incidence and various potential risk factors. The aim was to analyse the incidence and potential risk factors for PCF formation in a large study set collected over a longer period of time. In the retrospective study at the Department of Otorhinolaryngology and Cervicofacial Surgery of Ljubljana, 422 patients who were treated for head and neck cancer by TL between 2007 and 2020 were included. The comprehensive clinicopathologic data were collected including potential risk factors related to the patient, disease, surgical treatment and post-operative period for the development of fistulae. The patients were categorized into a group with the fistula (a study group) and one without it (a control group). The PCF then developed in 23.9% of patients. The incidence following a primary TL was 20.8% and 32.7% following salvage TL (p = 0.012). The results demonstrated that surgical wound infection, piriform sinus invasion, salvage TL, and total radiation dose were determined as independent risk factors for PCF formation. A diminishing surgical wound infection rate would contribute to a further reduction of the PCF rate.

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma.

Purpose: To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods: A review of the pertinent literature. Results: Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT. Conclusion: Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access.

Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells.

Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Management of Older Patients with Head and Neck Cancer: A Comprehensive Review.

The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.

Oral verrucous carcinoma: a diagnostic and therapeutic challenge.

BACKGROUND: Verrucous carcinoma is a low-grade variant of squamous cell carcinoma with specific morphologic, cytokinetic and clinical features. Despite low mitotic activity and slow growth, it can infiltrate adjacent tissues in advanced stages but does not metastasize. The most frequently affected site is the oral cavity. The following article provides latest updates in the etiology, clinical presentation, diagnostics and treatment options in oral verrucous carcinoma and discusses the existing dilemmas linked to this unique malignancy. CONCLUSIONS: Oral verrucous carcinoma must be differentiated from conventional squamous cell carcinoma due to its less aggressive behaviour with a more favourable prognosis. Close communication between clinician and pathologist is mandatory for making a correct diagnosis. Primary surgery with negative surgical margins seems to be the most successful treatment. However, management recommendations are not uniform since they are mostly based on case reports and small retrospective case series. Prospective and pooled multi-institutional studies are therefore needed.

HaN-Seg: The head and neck organ-at-risk CT and MR segmentation dataset.

PURPOSE: For the cancer in the head and neck (HaN), radiotherapy (RT) represents an important treatment modality. Segmentation of organs-at-risk (OARs) is the starting point of RT planning, however, existing approaches are focused on either computed tomography (CT) or magnetic resonance (MR) images, while multimodal segmentation has not been thoroughly explored yet. We present a dataset of CT and MR images of the same patients with curated reference HaN OAR segmentations for an objective evaluation of segmentation methods. ACQUISITION AND VALIDATION METHODS: The cohort consists of HaN images of 56 patients that underwent both CT and T1-weighted MR imaging for image-guided RT. For each patient, reference segmentations of up to 30 OARs were obtained by experts performing manual pixel-wise image annotation. By maintaining the distribution of patient age and gender, and annotation type, the patients were randomly split into training Set 1 (42 cases or 75%) and test Set 2 (14 cases or 25%). Baseline auto-segmentation results are also provided by training the publicly available deep nnU-Net architecture on Set 1, and evaluating its performance on Set 2. DATA FORMAT AND USAGE NOTES: The data are publicly available through an open-access repository under the name HaN-Seg: The Head and Neck Organ-at-Risk CT & MR Segmentation Dataset. Images and reference segmentations are stored in the NRRD file format, where the OAR filenames correspond to the nomenclature recommended by the American Association of Physicists in Medicine, and OAR and demographics information is stored in separate comma-separated value  files. POTENTIAL APPLICATIONS: The HaN-Seg: The Head and Neck Organ-at-Risk CT & MR Segmentation Challenge is launched in parallel with the dataset release to promote the development of automated techniques for OAR segmentation in the HaN. Other potential applications include out-of-challenge algorithm development and benchmarking, as well as external validation of the developed algorithms.