[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 · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary tumor volume and lymph node ADC1000 are predictors of survival.•CE-T1WI does not improve the prognostic capacity of DWI.•Using CE-T1WI for ROI placement results in lower interobserver agreement.
European Journal of Radiology 11/2014; 84(1). DOI:10.1016/j.ejrad.2014.10.015 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Radiotherapy and Oncology 11/2014; 113(2). DOI:10.1016/j.radonc.2014.10.008 · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Radiotherapy and Oncology 10/2014; 113(1). DOI:10.1016/j.radonc.2014.09.013 · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[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 · 4.67 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 · 4.86 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 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial. Experimental design: Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy (AR) and 171 to ARCON. Hemoglobin (Hb)-levels, measured before treatment, were defined as low when <7.5 mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed two years after inclusion of the last patient.
Pre-treatment Hb-levels were available and below normal in 27/173 (16%) AR and 27/167 (16%) ARCON patients. In patients with normal pre-treatment Hb-levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% vs 75%, P=0.44) and disease-free survival (DFS, 75% vs 70%, P=0.46) compared to AR. However, in patients with low pre-treatment Hb-levels ARCON significantly improved 5-year LRC (79% vs 53%, P=0.03) and DFS (68% vs 45%, P=0.04). In multivariate analysis including other prognostic factors, pre-treatment Hb remained prognostic for LRC and DFS in the AR treatment arm. No correlation between pre-treatment Hb-levels and pimonidazole uptake was observed.
Results from the randomized phase 3 trial support previous observations that ARCON has the potential to correct the poor outcome of anemic cancer patients. (ClinicalTrials.gov number, NCT00147732).
Clinical Cancer Research 01/2014; 20(5). DOI:10.1158/1078-0432.CCR-13-1730 · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retrospective studies indicate that larger tumour volume is a strong prognostic indicator for poor tumour control after (chemo)radiotherapy for laryngeal cancer. The impact of tumour volume on the outcome of patients treated within a prospective study comparing accelerated radiotherapy (AR)±carbogen breathing and nicotinamide (ARCON) was investigated.
Of 345 patients with cT2-4 laryngeal cancer, pre-treatment computed tomography (CT) scans of 270 patients were available for tumour volume calculation. Contouring of the primary tumour and involved lymph nodes was reviewed by one experienced head and neck radiation oncologist. Kaplan-Meier plots were used for analysis of outcome.
Of 137 AR and 133 ARCON patients, 57 and 80 versus 56 and 77 patients had glottic and supraglottic tumours, respectively. A correlation between primary tumour volume and T-stage was observed (Rs=.51, P<.01). In both treatment arms no correlation was detected between the primary tumour volume and local control (LC), regional control (RC) and metastasis-free survival (MFS). A strong correlation between total nodal volume and N-stage was found (Rs=.93, P<.01). Both in the AR and ARCON groups total nodal volume was not associated with poorer RC rate. However, based on individual lymph node analyses, nodal control was in favour of ARCON, irrespective of volume (P<.01).
Neither primary tumour volume, nor total nodal volume is a prognostic factor for patients with cT2-4 laryngeal cancer treated with accelerated radiotherapy±carbogen breathing and nicotinamide. Additional analyses based on individual nodal volumes demonstrate an excellent regional control rate and a significant benefit of ARCON.
European journal of cancer (Oxford, England: 1990) 01/2014; 50(6). DOI:10.1016/j.ejca.2013.12.012 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy (AR) in laryngeal carcinoma. Methods Labeling index of Ki-67 (Ki-67-LI) in immunohistochemically stained biopsies and the colocalization with CAIX were related to tumor control and patient survival. Results On average, node positive patients had a higher Ki-67-LI (median 14% vs 8% p<0.01). In patients with a high Ki-67-LI the 5-year regional control and metastases-free survival were 79% vs 96% (p<0.01) and 71% vs 88% (p=0.05), for AR and ARCON, respectively. The 5-year local control and disease-specific survival were not significantly different. Patients with low Ki-67 expression had an excellent outcome with AR alone. Conclusions Patients with larynx carcinomas with high proliferative activity are at increased risk of regional and distant metastases formation. This risk can be reduced by treatment with ARCON. Head Neck, 2013.
Head & Neck 12/2013; DOI:10.1002/hed.23569 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To retrospectively report changes in gross tumor volume (GTV) and organ-at-risk (OAR) doses after induction chemotherapy (IC) in oropharyngeal cancer using different contouring strategies.
GTV and OARs were delineated on pre- and post-IC planning CT. Two post-IC GTV contours were made: (1) a 'consensus set' using published guidelines (GTVconsensus), and (2) 'visible set', delineating only visible post-IC GTV (GTVvisible). Pre-IC interactively optimized volumetric modulated arc therapy plans were generated. The pre-IC planning constraints served as the starting point for both post-IC plans. Results reflect pooled data from all 10 patients.
Mean reduction in volume post-IC was 24% and 47% for consensus and visible primary tumor and 57% and 60% for consensus and visible nodes. Compared to pre-IC plans, average mean OAR dose for post-IC GTVconsensus plans was significantly lower for CL parotid. For GTVvisible plans both parotids, upper/lower larynx, inferior pharyngeal constrictor and cricopharyngeal muscles were significantly lower. However reductions compared with post-IC GTVconsensus plans were modest (1.6/1.5/1.2/3.7/5.9/2.6Gy, respectively).
IC in patients with oropharyngeal carcinoma results in substantial reductions in GTVs. If post-IC GTVs are used, which is contrary to current consensus, statistically significant but relatively small OAR dose reductions are observed.
Radiotherapy and Oncology 11/2013; 109(2). DOI:10.1016/j.radonc.2013.07.016 · 4.86 Impact Factor