Radiotherapy (RT) is one of the basic treatment modalities for cancer of the head and neck (H&N), which requires a precise spatial description of the target volumes and organs at risk (OARs) to ...deliver a highly conformal radiation dose to the tumor cells while sparing the healthy tissues. For this purpose, target volumes and OARs have to be delineated and segmented from medical images. As manual delineation is a tedious and time‐consuming task subjected to intra/interobserver variability, computerized auto‐segmentation has been developed as an alternative. The field of medical imaging and RT planning has experienced an increased interest in the past decade, with new emerging trends that shifted the field of H&N OAR auto‐segmentation from atlas‐based to deep learning‐based approaches. In this review, we systematically analyzed 78 relevant publications on auto‐segmentation of OARs in the H&N region from 2008 to date, and provided critical discussions and recommendations from various perspectives: image modality — both computed tomography and magnetic resonance image modalities are being exploited, but the potential of the latter should be explored more in the future; OAR — the spinal cord, brainstem, and major salivary glands are the most studied OARs, but additional experiments should be conducted for several less studied soft tissue structures; image database — several image databases with the corresponding ground truth are currently available for methodology evaluation, but should be augmented with data from multiple observers and multiple institutions; methodology — current methods have shifted from atlas‐based to deep learning auto‐segmentation, which is expected to become even more sophisticated; ground truth — delineation guidelines should be followed and participation of multiple experts from multiple institutions is recommended; performance metrics — the Dice coefficient as the standard volumetric overlap metrics should be accompanied with at least one distance metrics, and combined with clinical acceptability scores and risk assessments; segmentation performance — the best performing methods achieve clinically acceptable auto‐segmentation for several OARs, however, the dosimetric impact should be also studied to provide clinically relevant endpoints for RT planning.
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.
Abstract Aim To highlight the problems associated with nutrition that occur in patients with squamous cell carcinoma of the head and neck (SCCHN). Background SCCHN is associated with weight loss ...before, during and after radiotherapy or concurrent chemoradiotherapy. Because of serious consequences of malnutrition and cachexia on treatment outcome, mortality, morbidity, and quality of life, it is important to identify SCCHN patients with increased risk for the development of malnutrition and cachexia. Materials and methods Critical review of the literature. Results This review describes pathogenesis, diagnosis and treatment of malnutrition and cancer cachexia. Treatment of malnutrition and cancer cachexia includes nutritional interventions and pharmacological therapy. Advantages and disadvantages of different nutritional interventions and their effect on the nutritional status, quality of life and specific oncological treatment are presented. Conclusions Nutritional management is an essential part of care of these patients, including early screening, assessment of nutritional status and appropriate intervention.
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.
Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the ...response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC.
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•We organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge.•The task was to automatically segment of 30 OARs of the head and neck region.•The dataset ...consisted of 42 publicly available training and 14 withheld test cases.•Each case includes one CT and one MR image of the same patient with corresponding OAR reference delineations.•A total of seven teams participated by submitting their deep learning segmentation frameworks.
To promote the development of auto-segmentation methods for head and neck (HaN) radiation treatment (RT) planning that exploit the information of computed tomography (CT) and magnetic resonance (MR) imaging modalities, we organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge.
The challenge task was to automatically segment 30 organs-at-risk (OARs) of the HaN region in 14 withheld test cases given the availability of 42 publicly available training cases. Each case consisted of one contrast-enhanced CT and one T1-weighted MR image of the HaN region of the same patient, with up to 30 corresponding reference OAR delineation masks. The performance was evaluated in terms of the Dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95), and statistical ranking was applied for each metric by pairwise comparison of the submitted methods using the Wilcoxon signed-rank test.
While 23 teams registered for the challenge, only seven submitted their methods for the final phase. The top-performing team achieved a DSC of 76.9 % and a HD95 of 3.5 mm. All participating teams utilized architectures based on U-Net, with the winning team leveraging rigid MR to CT registration combined with network entry-level concatenation of both modalities.
This challenge simulated a real-world clinical scenario by providing non-registered MR and CT images with varying fields-of-view and voxel sizes. Remarkably, the top-performing teams achieved segmentation performance surpassing the inter-observer agreement on the same dataset. These results set a benchmark for future research on this publicly available dataset and on paired multi-modal image segmentation in general.
Purpose
To determine whether the psychological state of patients with head and neck cancer (HCN) is associated with their nutritional status.
Methods
In 40 patients with locally advanced HNC treated ...with definitive or adjuvant (chemo)radiotherapy, psychological and nutritional status were assessed before treatment, at its completion and 3 months’ post-therapy. Psychosocial distress was measured using the Hospital Anxiety and Depression Scale questionnaire (HADS-A, HADS-D), whereas the nutritional status was evaluated using standard methods (Nutritional Risk Screening Tool 2002, anthropometric data, dynamometry and laboratory tests) and with a bioelectrical impedance analysis parameter phase angle (PA).
Results
Before treatment, more patients were screened positive for anxiety than at treatment completion (
p
= 0.037) or 3 months’ post-therapy (
p
= 0.083). Depression prevalence was non-significantly higher at the end and after therapy. Compared to the baseline, more cachectic patients and a reduction of PA values were found at successive assessments. Anxiety was more often recorded among malnourished/cachectic patients (assessment 1,
p
= 0.017; assessment 2,
p
= 0.020) who were also found more frequently depressed (assessment 2,
p
= 0.045; assessment 3,
p
= 0.023). Significantly higher PA values were measured in patients without distress determined at 3 months’ post-therapy by the HADS-A (
p
= 0.027).
Conclusion
The association between the psychological and nutritional status found in this pilot study and the options for intervention warrants further clarification in a larger prospective trial.
Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southeast Asia, particularly Southern China. The classical non-keratinising cell type is almost unanimously associated with latent ...Epstein–Barr virus (EBV) infection. Circulating plasma EBV DNA can be a useful biomarker in various clinical aspects, but comprehensive recommendations and international guidelines are still lacking. We conducted a systematic review of all original articles on the clinical application of plasma EBV DNA for NPC; we further evaluated its strengths and limitations for consideration as standard recommendations.
The search terms ‘nasopharyngeal OR nasopharynx’, and ‘plasma EBV DNA OR cell-free EBV OR cfEBV’ were used to identify full-length articles published up to December 2020 in the English literature. Three authors independently reviewed the article titles, removed duplicates and reviewed the remaining articles for eligibility.
A total of 81 articles met the eligibility criteria. Based on the levels of evidence and grades of recommendation assessed, it is worth considering the inclusion of plasma EBV DNA in screening, pre-treatment work-up for enhancing prognostication and tailoring of treatment strategy, monitoring during radical treatment, post-treatment surveillance for early detection of relapse, and monitoring during salvage treatment for recurrent or metastatic NPC. One major limitation is the methodology of measurement requiring harmonisation for consistent comparability.
The current comprehensive review supports the inclusion of plasma EBV DNA in international guidelines in the clinical aspects listed, but methodological issues must be resolved before global application.
•Plasma Epstein–Barr virus DNA has been the most reliable and accurate marker in nasopharyngeal carcinoma management.•We provide evidence-based recommendations on its use in various clinical settings.•We support its inclusion in international guidelines in the aspects listed.•Limitations and methodological issues must be resolved before its global application.
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 (
= 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.
Abstract
Background
In head and neck cancer (HNC), the relationship between a delay in starting radiotherapy (RT) and the outcome is unclear. The aim of the present study was to determine the impact ...of the amount of time before treatment intervention (TTI) and the growth kinetics of individual tumors on treatment outcomes and survival.
Methods
Two hundred sixty-two HNC patients with 273 primary tumors, treated with definitive (chemo) RT, were retrospectively analyzed. The TTI was defined as the time interval between the date of histopathologic diagnosis and the first day of the RT course. Volumetric data on 57 tumors were obtained from diagnostic and RT planning computer tomography (CT) scans in order to calculate the tumor growth kinetic parameters.
Results
No significant association between locoregional control or cause-specific hazards and TTI was found. The log hazard for locoregional recurrence linearly increased during the first 40 days of waiting for RT, although this was not significant. The median tumor volume relative increase rate and tumor volume doubling time was 3.2%/day and 19 days, respectively, and neither had any impact on locoregional control or cause-specific hazards.
Conclusion
The association between a delay in starting RT and the outcome is complex and does not harm all patients waiting for RT. Further research into imaging-derived kinetic data on individual tumors is warranted in order to identify patients at an increased risk of adverse outcomes due to a delay in starting RT.