[Show abstract][Hide abstract] ABSTRACT: 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 24months 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.
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.
Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology; 08/2015
[Show abstract][Hide abstract] ABSTRACT: Treatment strategies for T3 laryngeal carcinoma include radiotherapy (RT) with or without chemotherapy (CT) and sometimes surgery. We conducted a national survey to determine how T3 laryngeal carcinoma is currently being managed in the Netherlands.
A questionnaire on general treatment policy, also inquiring details on RT and CT, was sent to all 13 radiotherapy departments accredited for treatment of head and neck cancer (HNC) in the Netherlands.
Twelve centers completed the questionnaire. All centers reported using RT with or without CT. Upfront laryngectomy is rarely performed. At 9/12 centers, CT is added to RT in cases with large tumors in T3N0 disease. Three centers use a volume criterion (3-6 cc); 6 centers don't specify "large" with such criteria. CT consists of cisplatin 3-weekly (7 centers) or weekly (2 centers), unless contra-indicated or age; 6 centers use an age limit of 70 years. RT is given concomitantly with CT 5×/week except at the 2 centers where cisplatin weekly is combined with 6 fractions/week. In case of RT only, treatment is accelerated. Lymph node levels II-IV are treated electively. In T3N+ disease, 11/12 centers treat non-bulky T3N1 with RT only. Volume criteria for combined CT-RT are the same as above. Two centers perform an upfront neck dissection in case of (resectable) N3 disease; 10 centers treat T3N2-3 cancer with primary CT-RT, 2 centers don't use the N-stage criterion. Total RT dose is 68-70 Gy, the elective dose varies between 46 and 57.75 Gy. Eight centers use a simultaneous integrated boost technique.
Treatment of T3 laryngeal cancer in the Netherlands is generally comparable, with CT-RT for voluminous T3N0 and most T3N+ tumors, but there are some differences between the centers in the use of chemotherapy and the dose-fractionation schemes. Therefore, the aim of the National Platform RT HNC is further standardization of RT dose, fractionation and delivery techniques.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs.
Archives of Oto-Rhino-Laryngology 06/2015; DOI:10.1007/s00405-015-3680-z · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications. Older patients selected for salvage surgery had a similar complication rate and survival as younger patients.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 06/2015; 35(3):162-72. · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT).
Pretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0-750s/mm(2) (ADC750) and 0-1000s/mm(2) (ADC1000). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC750 and ADC1000. Lesion volumes and ADC-values were related to DFS using Cox regression analysis.
Median follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75-0.83, respectively; lymph node: 0.81-0.83 and 0.61-0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P<0.001). Tumor volume (sensitivity: 73%; specificity: 57%) and lymph node ADC1000 (sensitivity: 71-79%; specificity: 77-79%) were independent significant predictors of DFS without and with including CE-T1WI (P<0.05).
Pretreatment primary tumor volume and lymph node ADC1000 were significant independent predictors of DFS in HNSCC treated with (C)RT. DFS could be predicted from ADC-values acquired without and with including CE-T1WI in image analysis. The inclusion of CE-T1WI did not result in significant improvements in the predictive value of DWI. DWI without including CE-T1WI was highly reproducible.
European Journal of Radiology 11/2014; 84(1). DOI:10.1016/j.ejrad.2014.10.015 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Different planning protocols may define varying planning target volume (PTV) dose criteria. We investigated the hypothesis that this could result in differences in organ-at-risk (OAR) sparing.
Material and methods:
Volumetric modulated arc therapy plans were created for ten locally advanced head and neck cancer patients following PTV criteria specified by the RTOG, EORTC and institutional (VUmc) protocols. Resulting plans were evaluated on the basis of the homogeneity index, calculated for the boost/elective PTVs as HIB/HIE=100%*(D2%-D98%)/D50% and mean dose to individual and composite salivary (compsal) and swallowing (compswal) OARs.
RTOG plans were the most homogeneous, with mean HIB of 8.2±0.9%, compared to 9.5±1.0%/11.6±1.5% for the VUmc/EORTC plans. EORTC plans provided most OAR sparing, with compsal/compswal doses of 24.6±7.7/22.9±4.2Gy, compared to 32.2±9.7/29.9±4.2Gy and 28.4±8.1/24.7±5.3Gy for RTOG and VUmc, respectively. EORTC provided 7.2/7.7Gy mean dose reductions to the contra/ipsilateral parotid glands compared to RTOG.
Different planning protocols resulted in different levels of PTV dose homogeneity. We observed differences of up to ⩾7Gy in composite and individual mean OAR doses. This could influence rates of toxicity and should be taken into account when comparing clinical studies. A consensus should be reached between major trial groups on appropriate PTV parameters.
Radiotherapy and Oncology 11/2014; 113(2). DOI:10.1016/j.radonc.2014.10.008 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 (TUBEM6) 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. TUBEM6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBEM6 as the endpoint.
The prevalence of TUBEM6 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.
We developed a multivariable NTCP model for TUBEM6 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.
Radiotherapy and Oncology 10/2014; 113(1). DOI:10.1016/j.radonc.2014.09.013 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Main problem:
Diffusion-weighted MRI (DW-MRI) has potential to predict chemoradiotherapy (CRT) response in head and neck squamous cell carcinoma (HNSCC) and is generally performed using echo-planar imaging (EPI). However, EPI-DWI is susceptible to geometric distortions. Half-fourier acquisition single-shot turbo spin-echo (HASTE)-DWI may be an alternative. This prospective pilot study evaluates the potential predictive value of EPI- and HASTE-DWI and 18F-fluorodeoxyglucose PET-CT (18F-FDG-PET-CT) early during CRT for locoregional outcome in HNSCC.
Eight patients with advanced HNSCC (7 primary tumors and 25 nodal metastases) scheduled for CRT, underwent DW-MRI (using both EPI- and HASTE-DWI) and 18F-FDG-PET(-CT) pretreatment, early during treatment and three months after treatment. Median follow-up time was 38 months.
No local recurrences were detected during follow-up. Median Apparent Diffusion Coefficient (ADC)EPI-values in primary tumors increased from 77×10(-5) mm(2)/s pretreatment, to 113×10(-5) mm(2)/s during treatment (P=0.02), whereas ADCHASTE did not increase (74 and 74 mm(2)/s, respectively). Two regional recurrences were diagnosed. During treatment, ADCEPI tended to be higher for patients with regional control [(117.3±12.1)×10(-5) mm(2)/s] than for patients with a recurrence [(98.0±4.2)×10(-5) mm(2)/s]. This difference was not seen with ADCHASTE. No correlations between ΔADCEPI and ΔSUV (Standardized Uptake Value) were found in the primary tumor or nodal metastases.
HASTE-DWI seems to be inadequate in early CRT response prediction, compared to EPI-DWI which has potential to predict locoregional outcome. EPI-DWI and 18F-FDG-PET-CT potentially provide independent information in the early response to treatment, since no correlations were found between ΔADCEPI and ΔSUV.
[Show abstract][Hide abstract] ABSTRACT: Curative radiotherapy or chemoradiation 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 prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients.
Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months).
Most important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001).
We established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6.
PLoS ONE 04/2014; 9(4):e94879. DOI:10.1371/journal.pone.0094879 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
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.
Journal of Medical Internet Research 03/2014; 16(3):e74. DOI:10.2196/jmir.2990 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and purpose
To evaluate the course of health-related quality of life (HRQOL) from diagnosis to 2 years 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 1 week before and 6 weeks and 6, 12, 18, and 24 months 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.
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.
The course of HRQOL of HNSCC patients during the first 2 years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite.
Radiotherapy and Oncology 03/2014; 110(3). DOI:10.1016/j.radonc.2014.01.002 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Conventional radiotherapy typically aims for homogenous dose in the planning target volume (PTV) while sparing organs at risk (OAR). The authors quantified and characterized the trade-off between PTV dose inhomogeneity (IH) and OAR sparing in complex head and neck volumetric modulated arc therapy plans.
Thirteen simultaneous integrated boost plans were created per patient, for ten patients. PTV boost(B)/elective(E) optimization priorities were systematically increased. IHB and IHE, defined as (100% - V95%) + V107%, were evaluated against the average of the mean dose to the combined composite swallowing and combined salivary organs (D-OARcomp). To investigate the influence of OAR size and position with respect to PTVB/E, OAR dose was evaluated against a modified Euclidean distance (DMB/DME) between OAR and PTV.
Although the achievable D-OARcomp for a given level of PTV IH differed between patients, excellent logarithmic fits described the D-OARcomp/IHB and IHE relationship in all patients (mean R(2) of 0.98 and 0.97, respectively). Allowing an increase in average IHB and IHE over a clinically acceptable range, e.g., from 0.4% ± 0.5% to 2.0% ± 2.0% and 6.9% ± 2.8% to 14.8% ± 2.7%, respectively, corresponded to a decrease in average dose to the composite salivary and swallowing structures from 30.3 ± 6.5 to 23.6 ± 4.7 Gy and 32.5 ± 8.3 to 26.8 ± 9.3 Gy. The increase in PTVE IH was mainly accounted for by an increase in V107, by on average 5.9%, rather than a reduction in V95, which was on average only 2%. A linear correlation was found between the OAR dose to composite swallowing structures and contralateral parotid and submandibular gland, with DME (R(2) = 0.83, 0.88, 0.95). Only mean ipsilateral parotid dose correlated with DMB (R(2) = 0.87).
OAR sparing is highly dependent on the permitted PTVB/E IH. PTVE IH substantially influences OAR doses. These results are relevant for clinical practice and for future automated treatment-planning strategies.
Medical Physics 02/2014; 41(2):021722. DOI:10.1118/1.4862521 · 2.64 Impact Factor