Patricia Doornaert

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (71)239.78 Total impact

  • Acta oncologica (Stockholm, Sweden) 12/2014; · 2.27 Impact Factor
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    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;
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    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;
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    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;
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    ABSTRACT: Background. Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a better survival than HPV-negative OPSCC. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) may also provide prognostic information. We evaluated glycolytic characteristics in HPV-negative and HPV-positive OPSCC.Methods. Forty-four patients underwent pretreatment 18F-FDG-PET-CT. Standardized Uptake Values (SUV) and metabolic active tumor volume (MATV) were determined for primary tumors. HPV-status was determined with p16 immunostaining, followed by high-risk HPV DNA detection on the positive cases.Results. Twenty-seven patients were HPV-positive (61.4%). Median MATV was 2.8 millilitres (ml) [1.6-5.1] for HPV-positive and 6.0 ml [4.4-18.7] for HPV-negative tumors (p<0.001). SUV-values are volume dependent (partial volume effect), therefore, MATV was included as covariate in multivariate analysis. The maximum SUV in HPV-positive was 3.9 units lower than in HPV-negative tumors (p=0.01).Conclusions. 18F-FDG-PET-CT parameters are lower in HPV-positive than in HPV-negative patients. Low pretreatment SUV-values in HPV-positive OPSCC may be at least partly explained by HPV-induced tumor changes. Head Neck, 2014
    Head & Neck 10/2014; · 2.83 Impact Factor
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    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.
    Quantitative imaging in medicine and surgery. 08/2014; 4(4):239-50.
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    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. · 2.91 Impact Factor
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    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. ( number, NCT00147732).
    Clinical Cancer Research 01/2014; · 7.84 Impact Factor
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    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; · 4.12 Impact Factor
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    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 01/2014; 16(3):e74. · 3.77 Impact Factor
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    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. 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 2 years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite.
    Radiotherapy and Oncology 01/2014; · 4.52 Impact Factor
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    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 01/2014; 9(4):e94879. · 3.53 Impact Factor
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    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; · 2.83 Impact Factor
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    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; · 4.52 Impact Factor
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    ABSTRACT: Background. Recently, the Quantitative Analysis of Normal Tissue Effect in the Clinic (QUANTEC) Group defined dose-volume constraints for the parotid glands to avoid severe xerostomia. The aim of this study was to determine if application of these QUANTEC criteria also protected against moderate-to-severe patient-rated xerostomia. Material and methods. The study population consisted of 307 head and neck cancer patients treated with primary (chemo)radiotherapy, either with 3D-CRT (56%) or with IMRT (44%). All patients participated in a standard follow-up program in which radiation-induced toxicity and quality of life were prospectively assessed. Patients who met the QUANTEC criteria were classified as low risk and otherwise as high risk. Results. In total, 41% of the patients (treated with 3D-CRT and IMRT) were classified as low risk patients. In the group treated with 3D-CRT and IMRT, it was possible to meet the QUANTEC criteria in 47% and 32% of the patients, respectively. Sparing the parotid glands with IMRT was considerably more difficult in patients with lymph node metastases and in patients with nasopharyngeal and oropharyngeal tumours. Low risk patients reported significantly less moderate-to-severe xerostomia than high risk patients. However, the predicted risk of elderly patients and patients with pre-existing minor patient-rated xerostomia at baseline was > 20%, even when the QUANTEC criteria were met. Conclusions. Significantly lower rates of radiation-induced patient-rated xerostomia were found among low risk patients treated according to the QUANTEC criteria, but these criteria do not completely protect against xerostomia. Particularly in elderly patients and patients already suffering from minor xerostomia at baseline, the QUANTEC criteria do not sufficiently protect against persistent, moderate-to-severe patient-rated xerostomia.
    Acta oncologica (Stockholm, Sweden) 09/2013; · 2.27 Impact Factor
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    ABSTRACT: Accelerated radiotherapy (AR) improves the poor prognosis associated with epidermal growth factor receptor (EGFR) overexpression frequently seen in head and neck carcinomas. Combining AR with carbogen and nicotinamide (ARCON) counteracts enhanced tumour cell proliferation- and hypoxia-related radioresistance. The purpose of this study was to investigate if EGFR expression levels are associated with response to ARCON in patients with carcinoma of the larynx. Patients (N=272) with advanced stage larynx carcinoma were randomised between AR alone and ARCON. Paraffin-embedded biopsies from these patients were processed for immunohistochemical staining of EGFR. EGFR fraction was quantitated by automated image analysis and related to clinical outcome. A large variation was observed in EGFR fraction between tumours with expression levels ranging from 0 to 0.93 (median fraction 0.4). No difference in 5-year locoregional control was found between low and high EGFR expressing tumours in the AR arm (69% versus 75%), which is in line with the established effect of AR in EGFR overexpressing tumours. There was, however, a significant association in the ARCON arm: patients with low EGFR levels had a better 5-year locoregional control (88% versus 72% p=0.02) and disease-specific survival (92% versus 77% p=0.01). ARCON improved locoregional control relative to AR only in patients with low EGFR expression (hazard ratio (HR) 0.34 p=0.009). In conclusion, only in tumours with a low EGFR fraction, adding hypoxia modification to AR has an additive beneficial effect on outcome. EGFR expression is a predictive biomarker for the selection of patients that will or will not respond to ARCON.
    European journal of cancer (Oxford, England: 1990) 07/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated. MATERIAL AND METHODS: 261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival. RESULTS: Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p<0.01 and MFS 92% vs 69%, p=0.06). Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (65% vs 84%, p=0.01, 70% vs 96%, p<0.01 and 42% vs 71%, p<0.01 respectively), and this could not be improved with ARCON. After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival. CONCLUSIONS: ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression. The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value.
    Radiotherapy and Oncology 05/2013; · 4.52 Impact Factor
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    ABSTRACT: 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.
    Oral Oncology 01/2013; 49(5):443-449. · 2.70 Impact Factor
  • Nutrition and Cancer 01/2013; · 2.70 Impact Factor
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    ABSTRACT: The authors prospectively assessed the independent association between weight loss and deterioration in quality of life (QOL) in patients treated by radiotherapy for head and neck cancer. In 533 head and neck cancer patients treated by curative radiotherapy, changes in weight and QOL were assessed between baseline (before radiotherapy) and follow-up (12 wk after the start of radiotherapy). Patients were categorized into 4 weight loss categories: 0%, 0.1%-5.0%, 5.1%-10.0%, and >10% weight loss. The association between weight loss and change in QOL was analyzed by linear regression analysis, adjusted for sociodemographic and tumor-related characteristics, and additionally for disease specific symptoms and tube feeding. Thirty percent of patients lost 0.1%-5.0% weight, 26% lost 5.1%-10.0% weight, and 24% lost >10% weight. Adjusted regression analyses showed a significant association between weight loss and deterioration of global QOL, physical functioning, social functioning, social eating, and social contact. After additional adjustment for disease-specific symptoms and tube feeding, weight loss (>10%) remained significantly associated with global QOL, social eating, and social contact (P < 0.05). More than 10% weight loss during and directly after radiotherapy has a significant impact on social eating, social contact, and QOL in head and neck cancer patients.
    Nutrition and Cancer 01/2013; 65(1):76-83. · 2.70 Impact Factor

Publication Stats

825 Citations
239.78 Total Impact Points


  • 2005–2014
    • VU University Medical Center
      • • Department of Radiation Oncology
      • • Department of Otolaryngology/Head and Neck Surgery
      Amsterdamo, North Holland, Netherlands
  • 2011–2013
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 2006–2013
    • University of Groningen
      • Department of Radiotherapy
      Groningen, Groningen, Netherlands
  • 2006–2012
    • VU University Amsterdam
      • • Department of Radiation Oncology
      • • Otolaryngology/Head & Neck Surgery Department
      Amsterdamo, North Holland, Netherlands
  • 2007
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands