Search

Background: The aim of this prospective cohort study was to investigate swallowing function in relation to personal and clinical factors among patients with head and neck cancer (HNC) from diagnosis up to 2 years after treatment. Methods: The 100 ml water swallow test was measured before treatment, and 3, 6, 12, and 24 months after treatment. Linear mixed‐effects model analysis was conducted to investigate changes over time and the association with personal (sex and age) and clinical (tumor site, tumor stage, and treatment modality) factors. Results: Among 128 included patients, number of swallows increased from baseline to 3 months after treatment and decreased to baseline again at 6 months after treatment. The number of swallows was associated with age and treatment modality. Conclusions: In patients with HNC, swallowing (dys)function changes over time with the worst score 3 months after treatment. A higher age and being treated with surgery are factors associated with swallowing dysfunction over time. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors. Methods: Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline. Results: Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels. Conclusion: Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Adaptive radiotherapy for head and neck cancer has become more routine due to an increase in imaging quality and improvement in radiation techniques. With the availability of faster adaptive workflows, it is possible to adapt more easily to (daily) changes. MRI offers besides great anatomical imaging, also functional information about the tumor and surrounding tissue. The aim of this review is to provide current state of evidence about target definition on MRI for adaptive strategies in the treatment of head and neck cancer. In recent years, MRI-guided radiotherapy (MRgRT) has taken an increasingly important position in image-guided radiotherapy (IGRT). Magnetic resonance imaging (MRI) offers superior soft tissue contrast in anatomical imaging compared to computed tomography (CT), but also provides functional and dynamic information with selected sequences. Due to these benefits, in current clinical practice, MRI is already used for target delineation and response assessment in patients with head and neck squamous cell carcinoma (HNSCC). Because of the close proximity of target areas and radiosensitive organs at risk (OARs) during HNSCC treatment, MRgRT could provide a more accurate treatment in which OARs receive less radiation dose. With the introduction of several new radiotherapy techniques (i.e., adaptive MRgRT, proton therapy, adaptive cone beam computed tomography (CBCT) RT, (daily) adaptive radiotherapy ensures radiation dose is accurately delivered to the target areas. With the integration of a daily adaptive workflow, interfraction changes have become visible, which allows regular and fast adaptation of target areas. In proton therapy, adaptation is even more important in order to obtain high quality dosimetry, due to its susceptibility for density differences in relation to the range uncertainty of the protons. The question is which adaptations during radiotherapy treatment are oncology safe and at the same time provide better sparing of OARs. For an optimal use of all these new tools there is an urgent need for an update of the target definitions in case of adaptive treatment for HNSCC. This review will provide current state of evidence regarding adaptive target definition using MR during radiotherapy for HNSCC. Additionally, future perspectives for adaptive MR-guided radiotherapy will be discussed. [ABSTRACT FROM AUTHOR]

Purpose: After treatment for head and neck cancer (HNC), patients often experience major problems in masticatory function. The aim of this prospective cohort study among patients with HNC was to investigate which personal and clinical factors are associated with masticatory function from diagnosis up to 2 years after treatment with curative intent. Methods: Masticatory function was measured using the Mixing Ability Test (MAT) before treatment (baseline), and 3, 6, 12, and 24 months after treatment. A linear mixed-effects model with a random intercept and slope was conducted to investigate changes over time and the association with personal (sex, age) and clinical (tumor site, tumor stage, treatment modality) factors as measured at baseline. Result: One-hundred-twenty-five patients were included. The prevalence of masticatory dysfunction was estimated at 29% at M0, 38% at M3, 28% at M6, 26% at M12, and 36% at M24. A higher (worse) MAT score was associated with age, tumor stage, tumor site, timing of assessment, and the interaction between assessment moment and tumor site. Conclusion: In patients with HNC, masticatory function changed over time and dysfunction was associated with a higher age, a tumor in the oral cavity, a higher tumor stage, and a shorter time since treatment. The prevalence of masticatory dysfunction ranged from 26 to 38%. [ABSTRACT FROM AUTHOR]

Purpose: Before and after treatment for head and neck cancer (HNC), many patients have problems with mastication, swallowing, and salivary flow. The aim of this study was to investigate the association between objective test outcomes of mastication, swallowing, and salivary flow versus patient-reported outcomes (PROs) measuring mastication-, swallowing-, and salivary flow–related quality of life. Methods: Data of the prospective cohort "Netherlands Quality of Life and Biomedical Cohort Study" was used as collected before treatment, and 3 and 6 months after treatment. Spearman's rho was used to test the association between objective test outcomes of the mixing ability test (MAT) for masticatory performance, the water-swallowing test (WST) for swallowing performance, and the salivary flow test versus PROs (subscales of the EORTC QLQ-H&N35, Swallow Quality of Life questionnaire (SWAL-QoL-NL) and Groningen Radiation-Induced Xerostomia (GRIX)). Results: Data of 142 patients were used, and in total, 285 measurements were performed. No significant correlations were found between the MAT or WST and subscales of the EORTC QLQ-H&N35. Significant but weak correlations were found between the MAT or WST and 4 subscales of the SWAL-QoL-NL. Weak to moderate correlations were found between the salivary flow test and GRIX at 3 and 6 months after treatment, with the highest correlation between salivary flow and xerostomia during the day (Spearman's rho = − 0.441, p = 0.001). Conclusion: The association between objective test outcomes and PROs is weak, indicating that these outcome measures provide different information about masticatory performance, swallowing, and salivary flow in patients with HNC. [ABSTRACT FROM AUTHOR]

A correction to the article "The course of swallowing problems in the first 2 years after diagnosis of head and neck cancer" is presented which appeared in the previous issue of the periodical.

: PurposeTo analyze the exact location of the most cranial metastatic cervical lymph node in patients with oropharyngeal or hypopharyngeal carcinoma. This was done to specify the cranial border of the elective nodal target volume for improvement of parotid-sparing irradiation.: Methods and materialsThe most cranial metastatic lymph node, ipsilateral and, when present, contralateral, was delineated on 58 diagnostic CT scans of patients with node-positive oropharyngeal or hypopharyngeal carcinoma. The distances from the delineated lymph node to the base of the skull were measured in all planes.: ResultsThe mean ipsilateral and contralateral distance to the base of the skull in the coronal plane was 25.6 mm (range 2.6–73.8; SD 14.7) and 34.7 mm (range 10.4–78.9; SD 14.0), respectively (p = 0.002). Ipsilateral and contralateral metastatic lymph nodes were located within 20 mm below the base of the skull in 24 patients (41%) and 3 patients (5%), respectively.: ConclusionContralateral metastatic lymph nodes are more caudally located than are ipsilateral metastatic lymph nodes. In elective irradiation, lowering the cranial border of the contralateral nodal target volume with 20 mm below the base of the skull should be considered. [Copyright &y& Elsevier]

Background: Treatment of patients with head and neck cancer can result in disrupted mastication. To measure masticatory performance in people with compromised mastication, the mixing ability test (MAT) was developed. Objective: In this study, the reliability of the MAT was evaluated in patients with head and neck cancer and healthy controls. Methods: Thirty‐four patients with head and neck cancer and 42 healthy controls performed the MAT twice on the same day. To assess reliability, the intra‐class correlation coefficient (ICC2,1), standard error of measurement (SEM), smallest detectable change (SDC) and limits of agreement (LoA) were calculated. Results: A good (ICC = 0.886) and moderate correlation (ICC = 0.525) were found for patients and healthy controls, respectively. Patients had a worse mixing ability (mean = 19.12, SD = 4.56) in comparison with healthy controls (mean = 16.42, SD = 2.04). The SEM was 0.76 in patients and 1.45 in healthy controls, with a SDC of 2.12 and 4.02, respectively. The LoA was −4.46 to 4.42 in patients and −3.65 to 4.59 in healthy controls. Conclusion: The MAT has a good reliability in patients with head and neck cancer and a moderate reliability in healthy controls. [ABSTRACT FROM AUTHOR]

Background: To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy. Methods: Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQH& N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured. Results: There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years followup. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01). Conclusion: Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio. [ABSTRACT FROM AUTHOR]

Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment.Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety).Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck.Trial Registration: ClinicalTrials.gov Identifier: NCT02442375 . [ABSTRACT FROM AUTHOR]

The article discusses a study aimed at determining the variation of tumor delineation among pathologists on H&E-sections for laryngeal and hyphpharyngeal carcinoma to quantify the uncertainties in the gold standard in the context of imaging validation studies for laryngeal and hypopharyngeal carcinoma. It suggests that delineation inaccuracies on images are larger than on histopathology.

Background and purpose.To determine the spatial correspondence between the gross tumor volume (GTV) delineated on computer tomography (CT) and the actual tumor on histopathology. Material and methods.Sixteen patients with T3 or T4 laryngeal or hypopharyngeal cancer underwent a CT scan before total laryngectomy. The GTV was delineated on CT by three independent observers and by consensus between the three observers. After surgery, whole-mount hematoxylin-eosin stained (H&E) sections were obtained. One pathologist delineated the tumor in the H&E sections (tumorH&E). The reconstructed specimen was registered to the CT scan in order to compare the GTV to the tumorH&Ein three dimensions. The overlap between the GTV and the tumorH&Ewas calculated and the distance between the volumes was determined. Results.Tumor tissue was delineated in 203 of 516 H&E sections. For 14 patients a detailed analysis could be performed. The GTV volume was on average 1.7 times larger than the volume of the tumorH&E. The mean coverage of the tumorH&Eby the consensus GTV was 88%. tumorH&Etissue was found at 1.6 mm to 12.9 mm distance outside the GTV depending on observer and patient. Conclusions.GTVs delineated on CT for laryngeal and hypopharyngeal cancer were 1.7 times larger than the tumor. Complete coverage of the tumor by the GTV was, however, not obtained. [ABSTRACT FROM AUTHOR]

Background: GTV delineation is the first crucial step in radiotherapy and requires high accuracy, especially with the growing use of highly conformal and adaptive radiotherapy techniques. If GTV delineations of observers concord, they are considered to be of high accuracy. The aim of the study is to determine the interobserver agreement for GTV delineations of supraglottic laryngeal carcinoma on CT and on CT combined with MR-images and to determine the effect of adding MR images to CT-based delineation on the delineated volume and the interobserver agreement. Methods: Twenty patients with biopsy proven T1-T4 supraglottic laryngeal cancer, treated with curative intent were included. For all patients a contrast enhanced planning CT and a 1.5-T MRI with gadolinium were acquired in the same head-and-shoulder mask for fixation as used during treatment. For MRI, a two element surface coil was used as a receiver coil. Three dedicated observers independently delineated the GTV on CT. After an interval of 2 weeks, a set of co-registered CT and MR-images was provided to delineate the GTV on CT. Common volumes (C) and encompassing volumes (E) were calculated and C/E ratios were determined for each pair of observers. The conformity index general (CIgen) was used to quantify the interobserver agreement. Results: In general, a large variation in interobserver agreement was found for CT (range: 0.29-0.77) as well as for CT-MR delineations (range: 0.17-0.80). The mean CIgen for CT (0.61) was larger compared to CT-MR (0.57) (p = 0.032). Mean GTV volume delineated on CT-MR (6.6 cm³) was larger compared to CT (5.6 cm³) (p = 0.002). Conclusion: Delineation on CT with co-registered MR-images resulted in a larger mean GTV volume and in a decrease in interobserver agreement compared to CT only delineation for supraglottic laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background GTV delineation is the first crucial step in radiotherapy and requires high accuracy, especially with the growing use of highly conformal and adaptive radiotherapy techniques. If GTV delineations of observers concord, they are considered to be of high accuracy. The aim of the study is to determine the interobserver agreement for GTV delineations of supraglottic laryngeal carcinoma on CT and on CT combined with MR-images and to determine the effect of adding MR images to CT-based delineation on the delineated volume and the interobserver agreement. Methods Twenty patients with biopsy proven T1-T4 supraglottic laryngeal cancer, treated with curative intent were included. For all patients a contrast enhanced planning CT and a 1.5-T MRI with gadolinium were acquired in the same head-and-shoulder mask for fixation as used during treatment. For MRI, a two element surface coil was used as a receiver coil. Three dedicated observers independently delineated the GTV on CT. After an interval of 2 weeks, a set of co-registered CT and MR-images was provided to delineate the GTV on CT. Common volumes (C) and encompassing volumes (E) were calculated and C/E ratios were determined for each pair of observers. The conformity index general (CIgen) was used to quantify the interobserver agreement. Results: In general, a large variation in interobserver agreement was found for CT (range: 0.29-0.77) as well as for CT-MR delineations (range: 0.17-0.80). The mean CIgen for CT (0.61) was larger compared to CT-MR (0.57) (p =0.032). Mean GTV volume delineated on CT-MR (6.6 cm3) was larger compared to CT (5.6 cm3) (p = 0.002). Conclusion Delineation on CT with co-registered MR-images resulted in a larger mean GTV volume and in a decrease in interobserver agreement compared to CT only delineation for supraglottic laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background and purpose: Since lymph nodes volumes are generally four times the volume of the primary PTV, the advantage of using tight margins around the primary PTV is not clear. Therefore treatment margins of T2-T4 laryngeal carcinoma for IMRT are generally chosen in such a way that the PTV is comparable to that in conventional radiotherapy. The aim of this study is to quantify the effect of volume reduction of the primary PTV of T2-T4 laryngeal carcinoma with regard to late toxicity despite elective irradiation of lymph node levels II to IV. Methods: Two treatment plans based on conservative (GTV-PTV = 15 mm and 20 mm cranial), and on evidence-based tight margins (GTV-PTV = 8 mm) were calculated for 16 patients. Toxicity effects were estimated based on the dose distributions. Results: Compared to conservative margins, using tight margins resulted in: 1) significant reduction of the normal tissue complication probability (NTCP) for swallowing muscles and submandibular glands, 2) significant reduction of the mean dose in all organs at risk (OAR), 3) a mean dose smaller than 60 Gy for all OARs except for the laryngeal cartilages. When the lymph node levels II to IV were prescribed with an elective dose, an NTCP reduction of 53% for the swallowing muscles and of 23% for the submandibular glands was found by using tight instead of conservative margins. When positive nodes were present, NTCP reduction amounted to 29% and 15%, respectively. Conclusions: There is a potential benefit in realizing evidence-based tight margins for laryngeal cancer patients despite elective irradiation of lymph node levels II to IV. [ABSTRACT FROM AUTHOR]

Background: The salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12 months after radiotherapy (RT) for head-and-neck cancer (HNC). Findings: Twenty-nine HNC patients with a residual stimulated SMG secretion rate of ?0.2 ml/10 min at 12 months after RT were analyzed. MUC5B (in U; normalized to 1) and total protein levels (mg/ml) were measured in SMG saliva at baseline and 12 months after RT using ELISA and BCA protein assay, respectively. Overall, median MUC5B levels decreased after RT from 0.12 to 0.03 U (p = 0.47). Patients were dichotomized into none/mild xerostomia (n = 12) and severe xerostomia (n = 17) based on a questionnaire completed at 12 months. SMG and whole saliva flow rates decreased after RT but were comparable in both groups. The median MUC5B level was higher in patients with no or mild xerostomia compared to patients with severe xerostomia (0.14 vs 0.01 U, p = 0.22). Half of the patients with severe xerostomia had no detectable MUC5B at 12 months after RT. No differences in total protein levels were observed. Conclusions: Qualitative saliva parameters like MUC5B need further investigation in RT-induced xerostomia. This pilot study showed a trend towards lower MUC5B levels in the SMG saliva of patients with severe xerostomia 12 months after RT for HNC. [ABSTRACT FROM AUTHOR]

: PurposeTo investigate the influence of the cranial border of electively irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D-CRT and IMRT).: Methods and materialsThe target volumes and organs at risk were delineated on the planning CT scans of 12 patients. Two elective target volumes were delineated. The first had the transverse process of the C1 atlas and the second had the transverse process of the C2 axis as cranial border of the Level II lymph nodes. 3D-CRT and IMRT planning were performed for both elective volumes, resulting in two plans per patient and technique, called the C1 and C2 plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and the contralateral up to C2 was also performed for IMRT. The normal tissue complication probability (NTCP) for xerostomia 1 year after RT was calculated using the parotid mean dose.: ResultsThe average mean dose ± standard deviation (SD) to the contralateral parotid gland was reduced from 33 ± 5 Gy for the IMRT C1 plans to 26 ± 4 Gy for the IMRT C2 plans and from 51 ± 6 Gy to 49 ± 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP ± SD for xerostomia was 38% ± 10% for IMRT C1 plans and 24% ± 6% for IMRT up to C2 on the contralateral side, regardless of which cranial border was irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value of 74% ± 12% and 71% ± 15% was obtained, respectively. The NTCP for xerostomia of the ipsilateral parotid gland was 53% ± 17% and 45% ± 20% for the IMRT C1 and C2 plans and 89% ± 11% and 87% ± 12% for the 3D-CRT C1 and C2 plans, respectively.: ConclusionLowering the cranial border of the Level II lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation, could be considered on the contralateral side when the risk of metastasis on that side is very low. This is especially true when IMRT is used, because the relative reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with conventional conformal RT up to C1. [Copyright &y& Elsevier]

Background and Purpose: Since lymph nodes volumes are generally four times the volume of the primary PTV, the advantage of using tight margins around the primary PTV is not clear. Therefore treatment margins of T2-T4 laryngeal carcinoma for IMRT are generally chosen in such a way that the PTV is comparable to that in conventional radiotherapy. The aim of this study is to quantify the effect of volume reduction of the primary PTV of T2-T4 laryngeal carcinoma with regard to late toxicity despite elective irradiation of lymph node levels II to IV.Methods: Two treatment plans based on conservative (GTV-PTV = 15 mm and 20 mm cranial), and on evidence-based tight margins (GTV-PTV = 8 mm) were calculated for 16 patients. Toxicity effects were estimated based on the dose distributions.Results: Compared to conservative margins, using tight margins resulted in: 1) significant reduction of the normal tissue complication probability (NTCP) for swallowing muscles and submandibular glands, 2) significant reduction of the mean dose in all organs at risk (OAR), 3) a mean dose smaller than 60 Gy for all OARs except for the laryngeal cartilages. When the lymph node levels II to IV were prescribed with an elective dose, an NTCP reduction of 53% for the swallowing muscles and of 23% for the submandibular glands was found by using tight instead of conservative margins. When positive nodes were present, NTCP reduction amounted to 29% and 15%, respectively.Conclusions: There is a potential benefit in realizing evidence-based tight margins for laryngeal cancer patients despite elective irradiation of lymph node levels II to IV. [ABSTRACT FROM AUTHOR]