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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]

Abstract Background Salivary gland function decreases after radiation doses of 39 Gy or higher. Currently, submandibular glands are not routinely spared. We implemented a technique for sparing contralateral submandibular glands (CLSM) during contralateral elective neck irradiation without compromising PTV coverage. Methods Volumetric modulated arc therapy (RapidArc™) plans were applied in 31 patients with stage II-IV HNC without contralateral neck metastases, all of whom received elective treatment to contralateral nodal levels II-IV. Group 1 consisted of 21 patients undergoing concurrent chemo-radiotherapy, with elective nodal doses of 57.75 Gy (PTVelect) and 70 Gy to tumor and pathological nodes (PTVboost) in 7 weeks. Group 2 consisted of 10 patients treated with radiotherapy to 54.45 Gy to PTVelect and 70 Gy to PTVboost in 6 weeks. All clinical plans spared the CLSM using individually adapted constraints. For each patient, a second plan was retrospectively generated without CLSM constraints ('non-sparing plan'). Results PTV coverage was similar for both plans, with 98.7% of PTVelect and 99.2% of PTVboost receiving ≥95% of the prescription dose. The mean CLSM dose in group 1 was 33.2 Gy for clinical plans, versus 50.6 Gy in 'non-sparing plans' (p < 0.001). In group 2, mean CLSM dose was 34.4 Gy for clinical plans, and 46.8 Gy for non-sparing plans (p = 0.002). Conclusions Elective radiotherapy to contralateral nodal levels II-IV using RapidArc consistently limited CLSM doses well below 39 Gy, without compromising PTV-coverage. Future studies will reveal if this extent of dose reduction can reduce patient symptoms.

• FDG-PET/CT-based nodal target volume definition improves regional control and survival. • No isolated recurrences in the electively treated neck occurred with FDG-PET/CT-based nodal target volume definition. • FDG-PET/CT-based nodal target volume definition causes target volume transformation. • FDG-PET/CT can guide gradient dose prescription with de-escalation of the elective dose. Multimodality imaging including 18F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV). Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed. FDG-PET/CT-based NTV was performed in 46% of the patients. The median follow-up was 31 months. Diagnostic imaging depicting the regional recurrence was co-registered with the initial CT-scan to reconstruct the exact site of the recurrence. Multivariate Cox regression analysis was performed to identify variables associated with radiotherapy outcome. FDG-PET/CT-based NTV improved control of disease in the CTV elective-nodal (HR: 0.33, p = 0.026), overall regional control (HR: 0.62, p = 0.027) and overall survival (HR: 0.71, p = 0.033) compared to CT-based NTV. The risk for recurrence in the CTV elective-nodal was increased in case of synchronous local recurrence of the primary tumor (HR: 12.4, p < 0.001). FDG-PET/CT-based NTV significantly improved control of disease in the CTV elective-nodal , overall regional control and overall survival compared to CT-based NTV. A significant proportion of CTV elective-nodal recurrences are potentially new nodal manifestations from a synchronous local recurrent primary tumor. These results support the concept of target volume transformation and give an indication of the potential of FDG-PET to guide gradual radiotherapy dose de-escalation in elective neck treatment in HNSCC. [ABSTRACT FROM AUTHOR]

Purpose: To develop and evaluate a patch‐based convolutional neural network (CNN) to generate synthetic computed tomography (sCT) images for magnetic resonance (MR)‐only workflow for radiotherapy of head and neck tumors. A patch‐based deep learning method was chosen to improve robustness to abnormal anatomies caused by large tumors, surgical excisions, or dental artifacts. In this study, we evaluate whether the generated sCT images enable accurate MR‐based dose calculations in the head and neck region. Methods: We conducted a retrospective study on 34 patients with head and neck cancer who underwent both CT and MR imaging for radiotherapy treatment planning. To generate the sCTs, a large field‐of‐view T2‐weighted Turbo Spin Echo MR sequence was used from the clinical protocol for multiple types of head and neck tumors. To align images as well as possible on a voxel‐wise level, CT scans were nonrigidly registered to the MR (CTreg). The CNN was based on a U‐net architecture and consisted of 14 layers with 3 × 3 × 3 filters. Patches of 48 × 48 × 48 were randomly extracted and fed into the training. sCTs were created for all patients using threefold cross validation. For each patient, the clinical CT‐based treatment plan was recalculated on sCT using Monaco TPS (Elekta). We evaluated mean absolute error (MAE) and mean error (ME) within the body contours and dice scores in air and bone mask. Also, dose differences and gamma pass rates between CT‐ and sCT‐based plans inside the body contours were calculated. Results: sCT generation took 4 min per patient. The MAE over the patient population of the sCT within the intersection of body contours was 75 ± 9 Hounsfield Units (HU) (±1 SD), and the ME was 9 ± 11 HU. Dice scores of the air and bone masks (CTreg vs sCT) were 0.79 ± 0.08 and 0.70 ± 0.07, respectively. Dosimetric analysis showed mean deviations of −0.03% ± 0.05% for dose within the body contours and −0.07% ± 0.22% inside the >90% dose volume. Dental artifacts obscuring the CT could be circumvented in the sCT by the CNN‐based approach in combination with Turbo Spin Echo (TSE) magnetic resonance imaging (MRI) sequence that typically is less prone to susceptibility artifacts. Conclusions: The presented CNN generated sCTs from conventional MR images without adding scan time to the acquisition. Dosimetric evaluation suggests that dose calculations performed on the sCTs are accurate, and can therefore be used for MR‐only radiotherapy treatment planning of the head and neck. [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]

Background: Total laryngectomy with or without adjuvant (chemo)radiation often induces speech, swallowing and neck and shoulder problems. Speech, swallowing and shoulder exercises may prevent or diminish these problems. The aim of the present paper is to describe the study, which is designed to investigate the effectiveness and cost-utility of a guided self-help exercise program built into the application "In Tune without Cords" among patients treated with total laryngectomy.Methods/design: Patients, up to 5 years earlier treated with total laryngectomy with or without (chemo)radiation will be recruited for participation in this study. Patients willing to participate will be randomized to the intervention or control group (1:1). Patients in the intervention group will be provided access to a guided self-help exercise program and a self-care education program built into the application "In Tune without Cords". Patients in the control group will only be provided access to the self-care education program. The primary outcome is the difference in swallowing quality (SWAL-QOL) between the intervention and control group. Secondary outcome measures address speech problems (SHI), shoulder disability (SDQ), quality of life (EORTC QLQ-C30, QLQ-H&N35 and EQ-5D), direct and indirect costs (adjusted iMCQ and iPCQ measures) and self-management (PAM). Patients will be asked to complete these outcome measures at baseline, immediately after the intervention or control period (i.e. at 3 months follow-up) and at 6 months follow-up.Discussion: This randomized controlled trial will provide knowledge on the effectiveness of a guided self-help exercise program for patients treated with total laryngectomy. In addition, information on the value for money of such an exercise program will be provided. If this guided self-help program is (cost)effective for patients treated with total laryngectomy, the next step will be to implement this exercise program in current clinical practice.Trial Registration: NTR5255 Protocol version 4 date September 2015. [ABSTRACT FROM AUTHOR]

Purpose: Interactive optimization during treatment planning requires intermittent adjustment of organ-at-risk (OAR) objectives relative to the dose-volume histogram line. This is a labor-intensive process and the resulting plans are prone to variations in quality. The authors' in-house developed approach to automated interactive optimization (AIO) automatically moves the mouse cursor to adjust the position of on-screen optimization objectives. This allows for the use of more objectives per OAR and results in a more frequent and consistent adjustment of these objectives during optimization. The authors report a detailed evaluation of AIO performance in support of its implementation for routine head and neck cancer (HNC) planning and an evaluation for locally advanced lungcancer (LC) planning which requires a different optimization strategy. Methods: Volumetric modulated arc therapy AIO plans (APs) were created for 70 HNC patients with a simultaneously integrated boost and 20 LC patients and benchmarked against their respective manually interactively optimized plans (MPs). The same set of optimization objectives and priorities was used for all APs, although planning target volume (PTV) optimization priorities could be increased manually in a subsequent "continue previous optimization" calculation. HNC plans were benchmarked using mean dose to individual and composite OARs and elective/boost PTV (PTVE/PTVB) volumes receiving 95% and 107% of the prescription dose (V95% and V107%, respectively). A clinician performed blinded comparison of 20 APs and respective MPs. LC plans were compared using PTV V95%/V107%, contralateral lung (CL) volume receiving 5 Gy (V5Gy), total lung (TL)-PTV V5Gy/V20Gy, and esophagus and heart V40Gy/V60Gy/mean doses. Results: For HNC, statistically significant improvements in sparing of all OARs, except for the ipsilateral submandibular gland and trachea, were obtained in the APs compared to MPs. Average mean dose to oral cavity, composite salivary, and swallowing structures were 25.4/23.8, 24.2/23.2, and 29.5/25.5 Gy, respectively, for the MPs/APs. PTV heterogeneity was similar: in the APs, PTVB V95% was 0.2% higher while PTV B/PTV E V107% was 0.4%/1.0% lower. In 19 out of 20 HNC patients, the clinician preferred the AP, mainly because of better OAR sparing and PTV dose homogeneity. For LC, APs had a significantly lower CL V5Gy (6.1%), heart mean dose/V60Gy (0.9 Gy/1.2%) and esophagus mean dose/V60Gy (0.9 Gy/2.8%), a nonsignificantly higher TL V20Gy (1.4%), and a slight, but significantly higher dose deposition to the body. PTV dose coverage and homogeneity were similar in the APs and MPs. AIO was considered sufficiently robust for clinical use in LC. Conclusions: HNC and LC APs were at least as good as, and often of improved quality over MPs. To date, AIO has been clinically implemented for HNC planning. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Weight loss is a frequently observed problem in patients with head and neck cancer (HNC) during radiotherapy. It is still to be assessed whether hypermetabolism is contributing to this problem. The aim of this study was to investigate hypermetabolism before radiotherapy, and changes in resting energy expenditure (REE) in HNC patients during radiotherapy. Methods: REE was measured by indirect calorimetry in 71 patients with HNC before radiotherapy, after 3 and 6 weeks of radiotherapy, and 3 months after radiotherapy. The association between REE and tumour stage, CRP, and prior tumour surgery was analyzed by linear regression analyses. Forty healthy control subjects were one-to-one matched to 40 patients by gender, age and fat free mass (FFM) index to compare REE. Results: Before radiotherapy, REE was not significantly different between patients and controls, neither in absolute values (1568 ± 247 vs. 1619 ± 244 kcal/d; p = 0.29), nor after weight-adjustment (22.1 ± 3.5 vs. 21.5 ± 3.3 kcal/kg, p = 0.42) or FFM-adjustment (31.5 ± 4.9 vs. 30.7 ± 4.5 kcal/kg, p = 0.38). REE was independent of tumour stage, CRP, and prior tumour surgery. REE (kcal/d) decreased during radiotherapy and thereafter by 9% from pre-radiotherapy (p < 0.01). Weight and FFM also decreased significantly over time (p < 0.001). REE adjusted for FFM decreased in the first 3 weeks of radiotherapy with 4% (B = −1.39 kcal/kg FFM, p < 0.01), increased at the end of radiotherapy and decreased again 3 months after radiotherapy (B = −1.31 kcal/kg FFM, p = 0.04). Conclusions: Head and neck cancer patients had normal REE before radiotherapy. During radiotherapy, REE decreased continuously with ongoing weight loss. However, weight loss is not the only explaining factor, since REE expressed per kg FFM showed a much more divergent course which is currently unexplained. [Copyright &y& Elsevier]

Background: Salivary gland function decreases after radiation doses of 39 Gy or higher. Currently, submandibular glands are not routinely spared. We implemented a technique for sparing contralateral submandibular glands (CLSM) during contralateral elective neck irradiation without compromising PTV coverage. Methods: Volumetric modulated arc therapy (RapidArc™) plans were applied in 31 patients with stage II-IV HNC without contralateral neck metastases, all of whom received elective treatment to contralateral nodal levels II-IV. Group 1 consisted of 21 patients undergoing concurrent chemo-radiotherapy, with elective nodal doses of 57.75 Gy (PTVelect) and 70 Gy to tumor and pathological nodes (PTVboost) in 7 weeks. Group 2 consisted of 10 patients treated with radiotherapy to 54.45 Gy to PTVelect and 70 Gy to PTVboost in 6 weeks. All clinical plans spared the CLSM using individually adapted constraints. For each patient, a second plan was retrospectively generated without CLSM constraints ('non-sparing plan'). Results: PTV coverage was similar for both plans, with 98.7% of PTVelect and 99.2% of PTVboost receiving ≥95% of the prescription dose. The mean CLSM dose in group 1 was 33.2 Gy for clinical plans, versus 50.6 Gy in 'nonsparing plans' (p < 0.001). In group 2, mean CLSM dose was 34.4 Gy for clinical plans, and 46.8 Gy for non-sparing plans (p = 0.002). Conclusions: Elective radiotherapy to contralateral nodal levels II-IV using RapidArc consistently limited CLSM doses well below 39 Gy, without compromising PTV-coverage. Future studies will reveal if this extent of dose reduction can reduce patient symptoms. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to evaluate the effectiveness and safety of our careful observational strategy and neck dissections and the accuracy of ultrasound-guided fine-needle aspiration cytology, and to determine the prognostic factors for outcome and regional control after primary chemoradiation. Diagnostic evaluation of the regional status after concurrent chemoradiation for advanced head and neck cancer remains difficult, and the indications for a salvage neck dissection and its extent are not clearly defined. Methods In a series of 540 patients, there was suspicion of regional residual or recurrent disease after chemoradiation in 61 patients who underwent 68 salvage neck dissections and 68 patients who were considered unresectable. For the patients with salvage neck dissection, the accuracy of ultrasound-guided fine-needle aspiration cytology was determined. Disease control in the neck, disease-specific and overall survival, and parameters that may have prognostic value for the outcome were evaluated. Results Neck dissection specimens contained viable tumor in 26 (43%) patients. Of these, 13 had selective neck dissections and 13 modified radical neck dissections. Ultrasound-guided fine-needle aspiration cytology had a sensitivity of 80% and specificity of 42%. Nine patients developed a regional recurrence after salvage neck dissection (5 located in contralateral neck). Five-year regional control and overall survival rates were 79% and 36%, respectively. Significant prognostic factors for overall survival were surgical margins and “residual versus recurrent disease” in multivariate analysis. Conclusion Considering the good regional control rate and the high rate of unnecessary neck dissections with a theoretical planned neck dissection strategy, we conclude that a careful observational strategy is worthwhile and safe. For the evaluation of radiation treatment response, ultrasound-guided fine-needle aspiration cytology has a low specificity. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Recently, we found that swallowing dysfunction after curative (chemo) radiation (CH) RT has a strong negative impact on health-related quality of life (HRQoL), even more than xerostomia. The purpose of this study was to design a predictive model for swallowing dysfunction after curative radiotherapy or chemoradiation. Materials and methods: A prospective study was performed including 529 patients with head and neck squamous cell carcinoma (HNSCC) treated with curative (CH) RT. In all patients, acute and late radiation-induced morbidity (RTOG Acute and Late Morbidity Scoring System) was scored prospectively. To design the model univariate and multivariate logistic regression analyses were carried out with grade 2 or higher RTOG swallowing dysfunction at 6 months as the primary (SWALL6months) endpoint. The model was validated by comparing the predicted and observed complication rates and by testing if the model also predicted acute dysphagia and late dysphagia at later time points (12, 18 and 24 months). Results: After univariate and multivariate logistic regression analyses, the following factors turned out to be independent prognostic factors for SWALL6months: T3–T4, bilateral neck irradiation, weight loss prior to radiation, oropharyngeal and nasopharyngeal tumours, accelerated radiotherapy and concomitant chemoradiation. By summation of the regression coefficients derived from the multivariate model, the Total Dysphagia Risk Score (TDRS) could be calculated. In the logistic regression model, the TDRS was significantly associated with SWALL6months ((p <0.001). Subsequently, we defined three risk groups based on the TDRS. The rate of SWALL6months was 5%, 24% and 46% in case of low-, intermediate- and high-risk patients, respectively. These observed percentages were within the 95% confidence intervals of the predicted values. The TDRS risk group classification was also significantly associated with acute dysphagia (P <0.001 at all time points) and with late swallowing dysfunction at 12, 18 and 24 months (p <0.001 at all time points). Conclusion: The TDRS is a simple and validated measure to predict swallowing dysfunction after curative (CH) RT for HNC. This classification system enables identification of patients who may benefit from strategies aiming at prevention of swallowing dysfunction after curative (CH) RT such as preventive swallowing exercises during treatment and/or emerging IMRT techniques aiming at sparing anatomical structures that are involved in swallowing. [Copyright &y& Elsevier]

Abstract: Background and purpose: In the present study, prognostic values of several CT-based pre-treatment nodal and treatment-related characteristics were evaluated among patients with squamous cell head and neck cancer treated with non-surgical modalities. Patients and methods: Included were 79 patients with 210 pathological nodes, who underwent primary irradiation or chemoradiation. Several nodal characteristics were assessed on the planning CT scan. In addition, the 3D-dose distribution in the nodes was calculated by the planning system to allow for evaluation of underdosage in the pathological nodes and to correlate these results with control in the neck. Analysis was done on patient level (regional control) and node level (nodal control). Results: For regional control, total nodal volume and the use of chemotherapy in addition to radiation were significant prognostic factors. For nodal control, also the presence of central necrosis and radiological extranodal spread were of importance. In case of radiotherapy alone, a minimal dose <95% of the prescribed dose was associated with worse control. In case of combined modality treatment, the minimal radiation dose was of less importance. Conclusions: Nodal volume and chemotherapy are the most important prognostic factors to control pathological nodes in the neck. Radiological central necrosis and extranodal growth, nodal volume and chemotherapy were significant prognostic factors for nodal control. Additionally, it appears that regional control in patients treated with primary radiation alone or with chemoradiation in case of a total nodal volume of more than 3.0cm3 results in an unacceptable high risk on regional recurrence. [Copyright &y& Elsevier]

Summary: The objective of this study was to investigate the prognostic significance of the hemoglobin (Hb) levels at different timepoints in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Included were 111 patients. The hemoglobin levels were assessed before surgery (PreS-Hb), between surgery and radiotherapy (HbAAC), before postoperative radiotherapy (PreRT-Hb) and at the end of radiotherapy (EndRT-Hb). HbAAC takes into account the duration of anemia during the interval between surgery and radiotherapy. Higher HbAAC corresponds with lower Hb levels. Five year locoregional control (LRC) among patients with HbAAC⩾median was 72% and significantly worse as compared to the 88% in case of HbAAC < median (p =0.0097). Multivariate analysis for LRC showed that the HbAAC was a prognostic factor. Overall survival (OS) after 3 years was 77% in case of HbAAC < median and 34% in case of HbAAC⩾median (p <0.0002). Multivariate analysis for OS showed that the PreS-Hb and HbAAC were prognostic factors. Hb level between surgery and radiotherapy is an important prognostic factor for both LRC and OS among patients with SCCHN treated with surgery and postoperative radiotherapy. [Copyright &y& Elsevier]

Background. The aim of the study was to analyze speech outcome for patients with advanced oral/oropharyngeal cancer treated with reconstructive surgery and adjuvant radiotherapy. Methods. Speech tests (communicative suitability, intelligibility, articulation, nasality, and consonant errors) were performed in a control group and in patients before treatment (n = 76), and 6 months (n = 51) and 12 months (n = 42) after treatment. Results. Speech tests were significantly worse for patients before and after treatment compared with the controls. Speech did not improve between 6 and 12 months. After treatment, patients with T3–4 tumors showed a significantly worse score for communicative suitability, intelligibility, and articulation than patients with T2 tumors. No significant differences were found for subsites after treatment, although patients with mobile tongue tumors showed the best results. Conclusion. Speech difficulties are significant, and with the knowledge of this study better counseling and vigilance as to speech difficulties may be possible in patients undergoing treatment for oral/oropharyngeal cancer. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

Background: During a 6-week course of (chemo)radiation many head and neck cancer patients have to endure radiotherapy-induced toxicity, negatively affecting patients' quality of life. Pretreatment counseling combined with self-help exercises could be provided to inform patients and possibly prevent them from having speech, swallowing, and shoulder problems during and after treatment. Objective: Our goal was to investigate the feasibility of a multimodal guided self-help exercise program entitled Head Matters during (chemo)radiation in head and neck cancer patients. Methods: Head and neck cancer patients treated with primary (chemo)radiation or after surgery were asked to perform Head Matters at home. This prophylactic exercise program, offered in three different formats, aims to reduce the risk of developing speech, swallowing, shoulder problems, and a stiff neck. Weekly coaching was provided by a speech and swallowing therapist. Patients filled out a diary to keep track of their exercise activity. To gain insight into possible barriers and facilitators to exercise adherence, reports of weekly coaching sessions were analyzed by 2 coders independently. Results: Of 41 eligible patients, 34 patients were willing to participate (83% uptake). Of participating patients, 21 patients completed the program (64% adherence rate). The majority of participants (58%) had a moderate to high level of exercise performance. Exercise performance level was not significantly associated with age (P=.50), gender (P=.42), tumor subsite (P=1.00) or tumor stage (P=.20), treatment modality (P=.72), or Head Matters format (Web-based or paper) (P=1.00). Based on patients' diaries and weekly coaching sessions, patients' perceived barriers to exercise were a decreased physical condition, treatment-related barriers, emotional problems, lack of motivation, social barriers, and technical problems. Patients' perceived facilitators included an increased physical condition, feeling motivated, and social and technical facilitators. Conclusions: Head Matters, a multimodal guided self-help exercise program is feasible for head and neck cancer patients undergoing (chemo)radiation. Several barriers (decreased physical condition, treatment-related barriers) and facilitators (increased physical condition, feeling motivated) were identified providing directions for future studies. The next step is conducting a study investigating the (cost-)effectiveness of Head Matters on speech, swallowing, shoulder function, and quality of life. [ABSTRACT FROM AUTHOR]

Objectives To identify patterns of long-term, radiation-induced swallowing dysfunction after definitive radiotherapy with or without chemotherapy (RT or CHRT) and to determine which factors may explain these patterns over time. Material and methods The study population consisted of 238 consecutive head and neck cancer patients treated with RT or CHRT. The primary endpoint was ⩾grade 2 swallowing dysfunction at 6, 12, 18 and 24 months after treatment. Cluster analysis was used to identify different patterns over time. The differences between the mean dose to the swallowing organs at risk for each pattern were determined by using dose maps. Results The cluster analysis revealed five patterns of swallowing dysfunction: low persistent, intermediate persistent, severe persistent, transient and progressive. Patients with high dose to the upper pharyngeal, laryngeal and lower pharyngeal region had the highest risk of severe persistent swallowing dysfunction. Transient problems mainly occurred after high dose to the laryngeal and lower pharyngeal regions, combined with moderate dose to the upper pharyngeal region. The progressive pattern was mainly seen after moderate dose to the upper pharyngeal region. Conclusions Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. Methods and Materials: A total of 288 patients with Stage I–IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. Results: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18–65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. Conclusions: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade ≥2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia. [Copyright &y& Elsevier]

Purpose The aim of this study was to clinically validate a multivariable normal tissue complication probability (NTCP) model for grade 2–4 swallowing dysfunction at 6 months after radiotherapy or chemoradiation (SWAL M6 ) in head and neck cancer patients treated with swallowing sparing intensity modulated radiotherapy (SW-IMRT) and to test if SW-IMRT resulted in a reduction of the prevalence of SWAL M6 . Materials and methods The primary endpoint was SWAL M6 . For all 186 patients, a standard IMRT (parotid sparing) and a SW-IMRT plan (additional constraints for swallowing organs at risk) was created. The difference in NTCP for SWAL M6 (ΔNTCP SWALM6 = NTCP standard − NTCP SW-IMRT ) was calculated. Patients were treated with SW-IMRT. The external validation of the NTCP model was analyzed by comparing performance measures. Results The mean ΔNTCP SWALM6 was 4.9% (range 0.01–17.3%), with a significant lower mean predicted NTCP SW-IMRT of 22.6% (95% CI 20.2–24.9%), compared to NTCP standard of 27.5% (95% CI 24.9–29.9%) ( p < 0.001). There was a perfect correspondence of NTCP SW-IMRT with the observed prevalence of SWAL M6 (22.6%). The overall model performance, discrimination and ‘goodness of fit’ were good. Conclusion We externally validated the multivariable NTCP model for SWAL M6 in SW-IMRT treated patients, showing reduced swallowing dysfunction by reducing the dose parameters included in this NTCP model. [ABSTRACT FROM AUTHOR]

Objectives: Patients with head and neck cancer (HNC) frequently encounter weight loss with multiple negative outcomes as a consequence. Adequate treatment is best achieved by early identification of patients at risk for critical weight loss. The objective of this study was to detect predictive factors for critical weight loss in patients with HNC receiving (chemo)radiotherapy ((C)RT).Materials and Methods: In this cohort study, 910 patients with HNC were included receiving RT (±surgery/concurrent chemotherapy) with curative intent. Body weight was measured at the start and end of (C)RT. Logistic regression and classification and regression tree (CART) analyses were used to analyse predictive factors for critical weight loss (defined as >5%) during (C)RT. Possible predictors included gender, age, WHO performance status, tumour location, TNM classification, treatment modality, RT technique (three-dimensional conformal RT (3D-RT) vs intensity-modulated RT (IMRT)), total dose on the primary tumour and RT on the elective or macroscopic lymph nodes.Results: At the end of (C)RT, mean weight loss was 5.1±4.9%. Fifty percent of patients had critical weight loss during (C)RT. The main predictors for critical weight loss during (C)RT by both logistic and CART analyses were RT on the lymph nodes, higher RT dose on the primary tumour, receiving 3D-RT instead of IMRT, and younger age.Conclusion: Critical weight loss during (C)RT was prevalent in half of HNC patients. To predict critical weight loss, a practical prediction tree for adequate nutritional advice was developed, including the risk factors RT to the neck, higher RT dose, 3D-RT, and younger age. [ABSTRACT FROM AUTHOR]

Background and purpose Curative radiotherapy/chemo-radiotherapy for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence 6 months (TUBE M6 ) after definitive radiotherapy, radiotherapy plus cetuximab or concurrent chemoradiation based on pre-treatment and treatment characteristics. Materials and methods The study included 355 patients with HNC. TUBE M6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBE M6 as the endpoint. Results The prevalence of TUBE M6 was 10.7%. The multivariable model with the best performance consisted of the variables: advanced T-stage, moderate to severe weight loss at baseline, accelerated radiotherapy, chemoradiation, radiotherapy plus cetuximab, the mean dose to the superior and inferior pharyngeal constrictor muscle, to the contralateral parotid gland and to the cricopharyngeal muscle. Conclusions We developed a multivariable NTCP model for TUBE M6 to identify patients at risk for tube feeding dependence. The dosimetric variables can be used to optimize radiotherapy treatment planning aiming at prevention of tube feeding dependence and to estimate the benefit of new radiation technologies. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To evaluate the course of health-related quality of life (HRQOL) from diagnosis to 2years follow-up in patients with head and neck cancer (HNSCC) treated with chemoradiation (CRT). Materials and methods: 164 patients completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 1week before and 6weeks and 6, 12, 18, and 24months after CRT. Patients were compared to a reference group. A linear mixed-model analysis was used to assess changes in HRQOL over time, and whether this was associated with age, gender, comorbidity, and tumor sublocation. Results: Significant differences for the majority of HRQOL scales were observed between patient and reference group at baseline, and follow-up. The course of HRQOL was different for survivors compared to non-survivors. In survivors, improvement over time was observed (in global quality of life, physical, role, and social function, fatigue, pain, swallowing, speech, social eating, and social contacts), while in non-survivors the pattern over time was either no changes in HRQOL or a deterioration (in physical function, social eating and contacts). In both survivors and non-survivors, emotional functioning improved after treatment, but deteriorated in the longer term. Patients with comorbidity reported worse physical function, and patients with oral/oropharyngeal cancer (compared to hypopharyngeal/laryngeal cancer) reported more oral pain and sexual problems, but fewer speech problems. Conclusions: The course of HRQOL of HNSCC patients during the first 2years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite. [Copyright &y& Elsevier]

Summary: Purpose: To evaluate long-term changes in health related quality of life (HRQOL) in oral/oropharyngeal cancer survivors and their need for and use of supportive care. Methods: Between 1999 and 2001, 80 advanced oral or oropharyngeal cancer patients treated with free-flap reconstruction and postoperative radiotherapy were included in a prospective study of whom 27 patients were long-term survivors (mean 9.2years, range 8–11years). The HRQOL of 26 patients (response rate 96%) was assessed with the EORTC QLQ-C30 and QLQ-H&N35 questionnaires at four points in time: pretreatment (baseline), and at 6months, 12months (short term) and 8–11years (long-term) follow up. A study specific questionnaire was developed to evaluate the need for and use of supportive care (allied health services, peer contact, psychosocial care, and complementary care) and was completed at the period of treatment and at long-term follow up. Results: A number of HRQOL domains worsened significantly (p <0.01) in the long-term: emotional functioning, social functioning, swallowing, speech, taste/smell, dry mouth, sticky saliva and coughing assessed by the mixed effects statistical model. At time of treatment, the need for supportive care was the highest for a dental hygienist (77%), a physical therapist (73%), a speech therapist (42%), a dietician (38%), and a special diet (62%). At long-term follow up, the need for supportive care was limited to a dental hygienist (46%) and a physical therapist (23%). Only small differences were observed between the perceived need for and actual use of supportive care. Conclusion: A range of HRQOL domains in head and neck cancer survivors were deteriorated in the long-term compared to baseline and to the first year after treatment. At time of treatment and less frequently at long-term follow up, patients reported needing and using a variety of supportive care services. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this multicentre prospective study was to develop multivariable logistic regression models to make valid predictions about the risk of moderate-to-severe patient-rated xerostomia (XERM6) and sticky saliva 6months (STICM6) after primary treatment with intensity modulated radiotherapy (IMRT) with or without chemotherapy for head and neck cancer (HNC). Methods and materials: The study population was composed of 178 consecutive HNC patients treated with IMRT. All patients were included in a standard follow up programme in which acute and late side effects and quality of life were prospectively assessed, prior to, during and after treatment. The primary endpoints were XERM6 and STICM6 as assessed by the EORTC QLQ-H&N35 after completing IMRT. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate-to-severe xerostomia or sticky saliva, respectively, at baseline were excluded. The optimal number of variables for a multivariate logistic regression model was determined using a bootstrapping method. Results: Eventually, 51.6% of the cases suffered from XERM6. The multivariate analysis showed that the mean contralateral parotid gland dose and baseline xerostomia (none vs. a bit) were the most important predictors for XERM6. For the multivariate NTCP model, the area under the receiver operating curve (AUC) was 0.68 (95% CI 0.60–0.76) and the discrimination slope was 0.10, respectively. Calibration was good with a calibration slope of 1.0. At 6months after IMRT, 35.6% of the cases reported STICM6. The mean contralateral submandibular gland dose, the mean sublingual dose and the mean dose to the minor salivary glands located in the soft palate were most predictive for STICM6. For this model, the AUC was 0.70 (95% CI 0.61–0.78) and the discrimination slope was 0.12. Calibration was good with a calibration slope of 1.0. Conclusions: The multivariable NTCP models presented in this paper can be used to predict patient-rated xerostomia and sticky saliva. The dose volume parameters included in the models can be used to further optimise IMRT treatment. [Copyright &y& Elsevier]

Abstract: Background and purpose: The purpose of this large multicentre prospective cohort study was to identify which dose volume histogram parameters and pre-treatment factors are most important to predict physician-rated and patient-rated radiation-induced swallowing dysfunction (RISD) in order to develop predictive models for RISD after curative (chemo) radiotherapy ((CH) RT). Material and methods: The study population consisted of 354 consecutive head and neck cancer patients treated with (CH) RT. The primary endpoint was grade 2 or more swallowing dysfunction according to the RTOG/EORTC late radiation morbidity scoring criteria at 6months after (CH) RT. The secondary endpoints were patient-rated swallowing complaints as assessed with the EORTC QLQ-H&N35 questionnaire. To select the most predictive variables a multivariate logistic regression analysis with bootstrapping was used. Results: At 6months after (CH) RT the bootstrapping procedure revealed that a model based on the mean dose to the superior pharyngeal constrictor muscle (PCM) and mean dose to the supraglottic larynx was most predictive. For the secondary endpoints different predictive models were found: for problems with swallowing liquids the most predictive factors were the mean dose to the supraglottic larynx and radiation technique (3D-CRT versus IMRT). For problems with swallowing soft food the mean dose to the middle PCM, age (18–65 versus >65years), tumour site (naso/oropharynx versus other sites) and radiation technique (3D-CRT versus IMRT) were the most predictive factors. For problems with swallowing solid food the most predictive factors were the mean dose to the superior PCM, the mean dose to the supraglottic larynx and age (18–65 versus >65years). And for choking when swallowing the V60 of the oesophageal inlet muscle and the mean dose to the supraglottic larynx were the most predictive factors. Conclusions: Physician-rated and patient-rated RISD in head and neck cancer patients treated with (CH) RT cannot be predicted with univariate relationships between the dose distribution in a single organ at risk and an endpoint. Separate predictive models are needed for different endpoints and factors other than dose volume histogram parameters are important as well. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). Methods and materials: The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. Results: The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. Conclusions: Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study was to investigate the ability of predictive models for patient-rated xerostomia (XER6M) and sticky saliva (STIC6M) at 6months after completion of primary (chemo)radiation developed in head and neck cancer patients treated with 3D-conformal radiotherapy (3D-CRT) to predict outcome in patients treated with intensity modulated radiotherapy (IMRT). Methods and materials: Recently, we published the results of a prospective study on predictive models for patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with 3D-CRT (3D-CRT based NTCP models). The 3D-CRT based model for XER6M consisted of three factors, including the mean parotid dose, age, and baseline xerostomia (none versus a bit). The 3D-CRT based model for STIC6M consisted of the mean submandibular dose, age, the mean sublingual dose, and baseline sticky saliva (none versus a bit). In the current study, a population consisting of 162 patients treated with IMRT was used to test the external validity of these 3D-CRT based models. External validity was described by the explained variation (R 2 Nagelkerke) and the Brier score. The discriminative abilities of the models were calculated using the area under the receiver operating curve (AUC) and calibration (i.e. the agreement between predicted and observed outcome) was assessed with the Hosmer–Lemeshow “goodness-of-fit” test. Results: Overall model performance of the 3D-CRT based predictive models for XER6M and STIC6M was significantly worse in terms of the Brier score and R 2 Nagelkerke among patients treated with IMRT. Moreover the AUC for both 3D-CRT based models in the IMRT treated patients were markedly lower. The Hosmer–Lemeshow test showed a significant disagreement for both models between predicted risk and observed outcome. Conclusion: 3D-CRT based models for patient-rated xerostomia and sticky saliva among head and neck cancer patients treated with primary radiotherapy or chemoradiation turned out to be less valid for patients treated with IMRT. The main message from these findings is that models developed in a population treated with a specific technique cannot be generalised and extrapolated to a population treated with another technique without external validation. [Copyright &y& Elsevier]

Abstract: Background and purpose: The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy. Materials and methods: Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale). Results: Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning. Conclusion: Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer. [Copyright &y& Elsevier]

Abstract: Background and purpose: In this prospective study, the effect of a second course of primary radiotherapy on locoregional control, survival and toxicity was investigated, in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma (HNSCC) in a previously irradiated area. Patients and methods: A total of 34 patients with second primary (n=26) or locoregional recurrent (n=8) tumours were treated with a second course of high dose radiotherapy. Patients were selected for re-irradiation in case of inoperable and/or unresectable tumours. In most cases, the target volume for re-irradiation was confined to the gross tumour volume (GTV). No elective radiotherapy was applied in the former high-dose area. A total dose of 46Gy was applied to elective areas with a boost up to 60Gy with conventional fractionation. The median follow-up period was 32 months. Results: The locoregional control rate after 2 years was 27%. The 3-year overall survival was 22%. The most frequently reported acute side-effect was acute mucositis resulting in swallowing complaints. Pharyngeal and oesophageal late morbidity was also the most important late side-effect. In general, acute and late radiation-induced morbidity remained within acceptable limits. Conclusions: In conclusion, primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity. To improve outcome in terms locoregional control and survival, future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy. [Copyright &y& Elsevier]

Objectives: The guided self-help exercise program called In Tune without Cords (ITwC) is effective in improving swallowing problems and communication among patients treated with a total laryngectomy (TL). This study investigated the cost-utility and cost-effectiveness of ITwC.Materials and Methods: Patients within 5 years after TL were included in this randomized controlled trial. Patients in the intervention group (n = 46) received access to the self-help exercise program with flexibility, range-of-motion and lymphedema exercises, and a self-care education program. Patients in the control group (n = 46) received access to the self-care education program only. Healthcare utilization (iMCQ), productivity losses (iPCQ), health status (EQ-5D-3L, EORTC QLU-C10D) and swallowing problems (SwalQol) were measured at baseline, 3- and 6-months follow-up. Hospital costs were extracted from medical files. Mean total costs and effects (quality-adjusted life-years (QALYs) or SwalQol score) were compared with regression analyses using bias-corrected accelerated bootstrapping.Results: Mean total costs were non-significantly lower (-€685) and QALYs were significantly higher (+0.06) in the intervention compared to the control group. The probability that the intervention is less costly and more effective was 73%. Sensitivity analyses with adjustment for baseline costs and EQ-5D scores showed non-significantly higher costs (+€119 to +€364) and QALYs (+0.02 to +0.03). A sensitivity analysis using the QLU-C10D to calculate QALYs showed higher costs (+€741) and lower QALYs (-0.01) and an analysis that used the SwalQol showed higher costs (+€232) and higher effects (improvement of 6 points on a 0-100 scale).Conclusion: ITwC is likely to be effective, but possibly at higher expenses.Trial Registration: NTR5255. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of a guided self-help exercise program on swallowing, speech, and shoulder problems in patients treated with total laryngectomy (TL).Materials and Methods: This randomized controlled trial included patients treated with TL in the last 5 years. Patients were randomized into the intervention group (self-help exercise program with flexibility, range-of-motion and lymphedema exercises and self-care education program) or control group (self-care education program). Both groups completed measurements before and 3 and 6-months after randomization. The primary outcome was swallowing problems (SWAL-QOL). Secondary outcomes were speech problems (SHI), shoulder problems (SDQ), self-management (patient activation: PAM) and health-related quality of life (HRQOL: EORTC QLQ-C30/H&N35). Adherence was defined as moderate-high in case a patient exercised >1 per day. Linear mixed model analyses were conducted to investigate the effectiveness of the intervention and to investigate whether neck dissection, treatment indication (primary/salvage TL), time since treatment, severity of problems, and preferred format (online/booklet) moderated the effectiveness.Results: Moderate-high adherence to the exercise program was 59%. The intervention group (n = 46) reported less swallowing and communication problems over time compared to the control group (n = 46) (p-value = 0.013 and 0.004). No difference was found on speech, shoulder problems, patient activation and HRQOL. Time since treatment moderated the effectiveness on speech problems (p-value = 0.025): patients within 6 months after surgery benefitted most from the intervention. Being treated with a neck dissection, treatment indication, severity of problems and format did not moderate the effectiveness.Conclusion: The guided self-help exercise program improves swallowing and communication.Trial Registration: NTR5255. [ABSTRACT FROM AUTHOR]