Johannes Langendijk
University of Groningen, Radiation Oncology, Faculty Member
This study investigated whether Magnetic Resonance image biomarkers (MR-IBMs) were associated with xerostomia 12 months after radiotherapy (Xer) and to test the hypothesis that the ratio of fat-to-functional parotid tissue is related to... more
This study investigated whether Magnetic Resonance image biomarkers (MR-IBMs) were associated with xerostomia 12 months after radiotherapy (Xer) and to test the hypothesis that the ratio of fat-to-functional parotid tissue is related to Xer. Additionally, improvement of the reference Xer model based on parotid gland dose and baseline xerostomia, with MR-IBMs was explored. Parotid gland MR-IBMs of 68 head and neck cancer patients were extracted from pre-treatment T1-weighted MR images, which were normalized to fat tissue, quantifying 21 intensity and 43 texture image characteristics. The performance of the resulting multivariable logistic regression models after bootstrapped forward selection was compared with that of the logistic regression reference model. Validity was tested in a small external cohort of 25 head and neck cancer patients. High intensity MR-IBM P90 (the 90th intensity percentile) values were significantly associated with a higher risk of Xer. High P90 values were re...
Research Interests: Magnetic Resonance Imaging, Biomarkers, Nuclear medicine, Adolescent, Medicine, and 15 moreLogistic Regression, Adipose tissue, Humans, Head and Neck Cancer, Female, Male, Head, Aged, Middle Aged, Adult, Parotid Gland, Intensity Modulated Radiotherapy, Logistic Models, Predictive value of tests, and Head and neck neoplasms
The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN) and how to minimize the likelihood of this complication. A PubMed search for publications pertaining to ORN within the last 3 years was... more
The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN) and how to minimize the likelihood of this complication. A PubMed search for publications pertaining to ORN within the last 3 years was conducted revealing 44 publications. The bibliographies of these publications were reviewed to identify additional references spanning a longer time period. The incidence of ORN is 5% to 10% with a median latency period of 1 to 2 years or less. The likelihood of ORN depends on a number of factors including primary site and extent of disease, dental status, treatment modality, radiotherapy (RT) dose, volume of mandible included in the planning target volume, RT fractionation schedule and technique, and teeth extractions. The risk of ORN may be reduced by limiting the RT dose and volume of mandible irradiated without increasing the risk of a local-regional recurrence due to a marginal miss.
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Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one... more
Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies. Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisi...
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Research Interests: Cancer, Radiation Therapy, Radiotherapy, Dysphagia, Medicine, and 15 moreHumans, Head and Neck Cancer, Female, Male, Mandible, Hearing Loss, Osteoradionecrosis, Radiation Injuries, Prognosis, Risk Assessment, Radiation Tolerance, Osteonecrosis, Disease Free Survival, Deglutition disorders, and Head and neck neoplasms
To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The... more
To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. The robustness criterion was met in the IMRT and minimax IMPT pla...
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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... more
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. 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. 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 (...
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Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there... more
Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there has been any measurable improvement for treatment outcomes. A retrospective review of data from recent studies that focus on surgery, radiation, and chemotherapy, or combinations thereof, was conducted. Surgery continues to be the preferred treatment and provides the best results, albeit with an inherent bias based on patient selection. For advanced disease (T4 lesions), the survival rate remains only modest. Complications of treatment, including both surgical and radiation therapy, have been reduced. There is a need to improve the efficacy of treatment for this disease. Recommendations for the future direction of therapeutic investigations are outlined.
Research Interests: Dentistry, Quality of life, Radiation Therapy, Medicine, Endoscopy, and 15 moreHead and Neck, Modalities, Humans, Head and Neck Cancer, Disease, Monoclonal Antibodies, Clinical Sciences, Head, Survival Rate, Nasal cavity, Antineoplastic Agents, Protein Kinase Inhibitors, Lymph nodes, Combined Modality Therapy, and Nose Neoplasms
7. Weiss D, Koopmann M, Rudack C. Prevalence and impact on clinicopa-thological characteristics of human papillomavirus-16 DNA in cervicallymph node metastases of head and neck squamous cell carcinoma.Head Neck 2011;33:856–862.8. Armas... more
7. Weiss D, Koopmann M, Rudack C. Prevalence and impact on clinicopa-thological characteristics of human papillomavirus-16 DNA in cervicallymph node metastases of head and neck squamous cell carcinoma.Head Neck 2011;33:856–862.8. Armas GL, Su CY, Huang CC, Fang FM, Chen CM, Chien CY. Theimpact of virus in N3 node dissection for head and neck cancer. EurArch Otorhinolaryngol 2008;265:1379–1384.9. Barwad A, Sood S, Gupta N, Rajwanshi A, Panda N, Srinivasan R.Human papilloma virus associated head and neck cancer: a PCR basedstudy. Diagn Cytopathol 2011;Epub ahead of print.10. Hoffmann M, Gottschlich S, G€or €ogh T, et al. Human papillomaviruses inlymph node neck metastases of head and neck cancers. Acta Otolaryngol2005;125:415–421.11. Desai PC, Jaglal MV, Gopal P, et al. Human papillomavirus in metastaticsquamous carcinoma from unknown primaries in the head and neck: a ret-rospective 7 year study. Exp Mol Pathol 2009;87:94–98.12. Compton AM, Moore-Medlin T, Herman-Ferdinandez L, et al. Humanpapillomavirus in metastatic lymph nodes from unknown primary headand neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2011;145:51–57.
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Research Interests: Dentistry, Cancer, Medicine, HUMAN PAPILLOMAVIRUS, Humans, and 15 moreHead and Neck Cancer, Female, Male, Clinical Sciences, Head, Aged, Middle Aged, Prognosis, Chemoradiotherapy, Lymph Node, Intensity Modulated Radiotherapy, Lymph nodes, Disease Free Survival, Neck dissection, and Head and neck neoplasms
Research Interests: Radiology, Magnetic Resonance Imaging, Radiation Therapy, Medicine, Head and Neck, and 11 moreHumans, Squamous Cell Carcinoma, Psychosocial, HPV, Multimodal imaging, Clinical Sciences, Oral Squamous Cell Carcinoma (OSCC), Time Factors, X ray Computed Tomography, Neoplasm metastasis, and Head and neck neoplasms
Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and... more
Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the rehabilitation process, and to provide psychosocial support when needed. To our knowledge, there are no published reports in the literature dedicated to the follow-up of patients with these tumours. A comprehensive literature search for post-treatment follow-up strategies spanning from 1980 to 2012 was performed on several databases. This review focuses on malignant salivary gland tumors, soft tissue sarcomas, cutaneous squamous cell carcinomas, and sinonasal adenocarcinomas. Given the varying biological behavior and treatment-related factors and based on the literature, different recommendations are made on the follow-up of patients with the above-mentioned tumors.
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Research Interests: Surgery, Cancer, Quality of life, Radiation Therapy, Medicine, and 15 moreProspective studies, Humans, Head and Neck Cancer, Female, Male, Head and neck squamous cell carcinoma, Risk factors, Aged, Middle Aged, Carcinoma, Adult, Radiation Injuries, Risk Factors, Combined Modality Therapy, and Head and neck neoplasms
Research Interests: Radiation Therapy, Nuclear medicine, Prostate Cancer, Radiotherapy, Medicine, and 15 moreLogistic Regression, Humans, Computer Simulation, Male, Prostate, Aged, Middle Aged, Carcinoma, Adult, ACTA, Radiation Injuries, Risk Factors, Receiver Operating Characteristic, Age of Onset, and Confidence Interval
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A risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are most at risk to develop grade ⩾2 dysphagia at 6months following radiotherapy (RT) for head and neck cancer. The purpose of this study was to... more
A risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are most at risk to develop grade ⩾2 dysphagia at 6months following radiotherapy (RT) for head and neck cancer. The purpose of this study was to validate this model at 6months and to investigate the power at earlier and later time-points. A second aim was to see if this model can be used in a partially accelerated RT regimen. 164 patients from 3 different centres treated with RT between 2008 and 2014 were included in the current study. Both physician-scored dysphagia and QoL data were prospectively obtained. The TDRS of all patients was correlated with the physician-scored dysphagia and the QoL data. To validate this prediction model, we tested the validity in terms of calibration and discrimination. Partial acceleration had no influence on the TDRS. Regarding physician-scored dysphagia, there was a significant correlation with dysphagia grade ⩾2 at 1, 3, 6 and 9months. The area-under-the-curve at 1month was 0.85; at 3months 0.80; at 6months 0.85; at 9months 0.86 and 0.79 at 12months. Regarding QoL, TDRS correlates with PEG-tube usage at 6 and 12months. We found significant correlations between TDRS and dysphagia grade ⩾2 and PEG-tube usage.
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Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the... more
Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.
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Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment... more
Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region...
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Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Dutch scientific and health care governance bodies have recently... more
Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.
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(18)F-fluoroazomycinarabinoside ((18)F-FAZA) is a promising hypoxia radiopharmaceutical agent with outstanding biokinetic parameters. We aimed to determine the accuracy of (18)F-FAZA-PET/CT scan in detecting hypoxic regions within the... more
(18)F-fluoroazomycinarabinoside ((18)F-FAZA) is a promising hypoxia radiopharmaceutical agent with outstanding biokinetic parameters. We aimed to determine the accuracy of (18)F-FAZA-PET/CT scan in detecting hypoxic regions within the tumor using immunohistochemical markers in a pilot study. Eleven patients with primary or recurrent laryngeal squamous cell carcinoma were indicated for total laryngectomy (TLE). Patients underwent (18)F-FAZA-PET/CT scan before TLE. Hypoxic regions inside the laryngeal tumor were determined. After TLE, regions with high uptake on (18)F-FAZA-PET scan were selected for immunohistochemical examination for exogenous (pimonidazole) and endogenous (HIF1α, CA-IX and GLUT-1) hypoxia markers. To assess the accuracy of (18)F-FAZA-PET scanning, radiopharmacon accumulation was related with immunohistochemical expression of hypoxia markers. Inter- and intratumoral heterogeneity of tumor hypoxia was observed on (18)F-FAZA-PET scan. Nine of the eleven tumors were hypoxic with (18)F-FAZA-PET. Hypoxia could also be detected with pimonidazole, HIF1α, CA-IX and GLUT-1 expression in some tumors. No clear association was observed between (18)F-FAZA uptake and hypoxia markers. This pilot study could not prove the accuracy of (18)F-FAZA-PET in determining hypoxic subvolumes in laryngeal cancer. Further study is required to investigate the benefit of (18)F-FAZA-PET imaging in radiotherapy planning.
A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this... more
A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT.
The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. Consensus guidelines were formulated based on... more
The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1mm axial slices. The atlas can also be obtained in DICOM-RT format on request. Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers.
Background and aims: Head and neck cancer patients (HNCP) are at risk for weight loss during treatment, due to oral sequalae of cancer treatment, e.g., mucositis and swallowing problems, dental problems, and trismus. Loss of fat free mass... more
Background and aims: Head and neck cancer patients (HNCP) are at risk for weight loss during treatment, due to oral sequalae of cancer treatment, e.g., mucositis and swallowing problems, dental problems, and trismus. Loss of fat free mass (FFM) reduces immune function and quality of life. To determine whether weight loss during treatment consists of loss of fat mass and/or FFM, we measured body composition prospectively. Methods: Adult patients with squamous cell carcinoma in the oral cavity, pharynx, or larynx and undergoing surgery plus radiotherapy, radiotherapy, or chemoradiation with curative intent were included. All patients received dietary intervention during treatment. Only patients treated with chemoradiation (n=4) received prophylactic gastrostomy placement. Fat mass and FFM were measured by dual energy X-ray absorptiometry, before treatment (T0) and after treatment (T1). Paired samples t test was used to analyze changes in FFM and fat mass between T0 and T1. In total, 3...
Background and aims: Already at diagnosis, head and neck cancer patients are at risk for malnutrition. Local symptoms, such as swallowing problems are a major cause of malnutrition in these patients. Additionally, malnutrition may result... more
Background and aims: Already at diagnosis, head and neck cancer patients are at risk for malnutrition. Local symptoms, such as swallowing problems are a major cause of malnutrition in these patients. Additionally, malnutrition may result from changes in smell and taste/aversion and loss of appetite 1 . Presence of these systemic symptoms at diagnosis may be indicative for the cachexia syndrome. Therefore, we tested the hypothesis that head and neck cancer patients suffer from cachexia. Methods: Twenty-six adult patients (21 male and 5 female) with newly diagnosed squamous cell carcinoma in the oral cavity (n=9), pharynx (n=11) or larynx (n=6), using a solid diet, were included. Cachexia was assessed 1 week prior to start of cancer treatment, according to the criteria of Fearon et al. 2 : appendicular skeletal muscle index <7.26 kg/m² in men and <5.45 kg/m² in women, as measured by dual energy X-ray absorptiometry, and any degree of weight loss >2%. Additionally, inflammator...
In the last decade, many efforts have been made to characterize anatomic changes of head and neck organs at risk (OARs) and the dosimetric consequences during radiotherapy. This review was undertaken to provide an overview of the... more
In the last decade, many efforts have been made to characterize anatomic changes of head and neck organs at risk (OARs) and the dosimetric consequences during radiotherapy. This review was undertaken to provide an overview of the magnitude and frequency of these effects, and to investigate whether we could find criteria to identify head and neck cancer patients who may benefit from adaptive radiotherapy (ART). Possible relationships between anatomic and dosimetric changes and outcome were explicitly considered. A literature search according to PRISMA guidelines was performed in MEDLINE and EMBASE for studies concerning anatomic or dosimetric changes of head and neck OARs during radiotherapy. Fifty-one eligible studies were found. The majority of papers reported on parotid gland (PG) anatomic and dosimetric changes. In some patients, PG mean dose differences between planning CT and repeat CT scans up to 10Gy were reported. In other studies, only minor dosimetric effects (i.e. <1Gy...
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To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system. Twenty HNC patients were... more
To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system. Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle(3)). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1-5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC). In total, the radiation-oncologists rated 800 items on plan quality. The ...
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As a result of longer survival times, even among patients with incurable malignancies, the probability of developing second primary tumours and/or locoregional recurrences in previously irradiated areas might increase. Consequently, the... more
As a result of longer survival times, even among patients with incurable malignancies, the probability of developing second primary tumours and/or locoregional recurrences in previously irradiated areas might increase. Consequently, the need for additional therapeutic measures providing local control and/or symptom palliation along different lines of treatment has emerged. This has resulted in increasing requests for delivering a second course
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To assess and compare brain abnormalities on Magnetic Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients treated with or without postoperative radiotherapy (RT). In 86 NFA patients, treated between 1987 and... more
To assess and compare brain abnormalities on Magnetic Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients treated with or without postoperative radiotherapy (RT). In 86 NFA patients, treated between 1987 and 2008 at the University Medical Center Groningen, white-matter lesions (WMLs), cerebral atrophy, brain infarctions and abnormalities of the temporal lobes and hippocampi were assessed on pre- and post-treatment MRI scans in patients treated with (n=47) or without RT. The median MRI follow-up time for RT patients was 10 (range 1-22) years and 5 (range 1-21) years in patients treated without RT. In RT patients the cumulative incidence of WMLs was significantly lower compared to patients treated without RT (log-rank test RR 0.49, 95% CI 0.25-0.97, p=.042). The cumulative incidences of cerebral atrophy, brain infarctions, abnormalities of the temporal lobes and hippocampi, and the severity of WMLs and cerebral atrophy ratings were not significantly diffe...
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PurposeThe phase III 22071¿26071 trial was designed to evaluate the addition of panitumumab to adjuvant chemotherapy plus intensity modulated radiotherapy (IMRT) in locally advanced resected squamous cell head and neck cancer. We report... more
PurposeThe phase III 22071¿26071 trial was designed to evaluate the addition of panitumumab to adjuvant chemotherapy plus intensity modulated radiotherapy (IMRT) in locally advanced resected squamous cell head and neck cancer. We report the results of the dummy run (DR) performed to detect deviations from protocol guidelines.Methods and MaterialsDR datasets consisting of target volumes, organs at risk (OAR) and treatment plans were digitally uploaded, then compared with reference contours and protocol guidelines by six central reviewers. Summary statistics and analyses of potential correlations between delineations and plan characteristics were performed.ResultsOf 23 datasets, 20 (87.0%) GTVs were evaluated as acceptable/borderline, along with 13 (56.5%) CTVs and 10 (43.5%) PTVs. All PTV dose requirements were met by 73.9% of cases. Dose constraints were met for 65.2-100% of mandatory OARs. Statistically significant correlations were observed between the subjective acceptability of ...
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Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We... more
Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We analysed consecutive patients referred via a university-hospital based multidisciplinary team. Patients were offered PME as first choice and SABR in case they were considered to be less suitable surgical candidates. Overall survival was the primary endpoint. Secondary endpoints were progression-free-survival, local control of treated metastases, and freedom-from-failure of a local-only treatment strategy without systemic therapy. From 2007 until 2010, 110 patients were treated and analysed (PME, n=68; SABR, n=42). Median follow-up time was 43 months (minimally, 25). Estimated overall survival rates at one, three, and five years were 87%, 62%, and 41% for PME, and 98%, 60%, and 49% for SABR, respectively (logrank-test, p=0.43). Local control at two yea...
Research Interests: Radiosurgery, Adolescent, Humans, Female, Male, and 4 moreAged, Middle Aged, Adult, and Survival Rate
Background. The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for non-metastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods. The... more
Background. The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for non-metastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols vs. radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for non-nasopharyngeal HNSCC was extracted. In the case of non-randomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Results. Eleven randomized trials and 7 non-randomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p=0.027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Conclusion. Results support the conclusion that the cumulative dos...
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Research Interests: Adolescent, Prospective studies, Humans, Female, Male, and 5 moreAged, Middle Aged, Adult, Parotid Gland, and Cohort Studies
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In 2005, we introduced hypofractionated 3-dimensional conformal radiotherapy with a simultaneous integrated boost (3D-CRT-SIB) technique after breast conserving surgery. In a consecutive series of 752 consecutive female invasive breast... more
In 2005, we introduced hypofractionated 3-dimensional conformal radiotherapy with a simultaneous integrated boost (3D-CRT-SIB) technique after breast conserving surgery. In a consecutive series of 752 consecutive female invasive breast cancer patients (stages I-III) the 5-year actuarial rate for local control was 98.9%. This new technique gives excellent 5-year local control.
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Research Interests: Quality of life, Treatment Outcome, Risk assessment, Probability, Prospective studies, and 21 moreHumans, Head and Neck Cancer, Female, Male, Confidence intervals, Aged, Prevalence, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Saliva, Adult, Radiation Dose, Mouth, Survival Rate, Xerostomia, Radiation Injuries, Risk Assessment, Oral Cavity, Salivary Gland, Logistic Models, and Salivary Glands
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... more
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. 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 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation. The median follow-up period was 32 months. 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. 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.