Jan Roodenburg

Detection of unknown occult primary tumors using positron emission tomography

The potential of positron emission tomography (PET) with 18F‐fluoro‐2‐deoxy‐D‐glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor.

Protocol for the Prevention and Treatment of Oral Sequelae Resulting from Head and Neck Radiation Therapy

In addition to the desired antitumor effects, head and neck radiation therapy induces damage in normal tissues that may result in oral sequelae such as mucositis, hypo‐salivation, radiation caries, taste loss, trismus, soft‐tissue necrosis, and osteoradionecrosis. These sequelae may be dose‐limiting and have a tremendous effect on the patients quality of life, Current policies to prevent these sequelae primarily are based on clinical experience and show great diversity. A protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy, based on fundamental research and data derived from the literature, is presented. The protocol is particularly applicable in centers with a dental team. This team should be involved at the time of initial diagnosis so that a successful preventive regimen is an integral part of the overall cancer treatment regimen.

Preventive Intervention Possibilities in Radiotherapy- and Chemotherapy-induced Oral Mucositis: Results of Meta-analyses

The aim of these meta-analyses was to evaluate the effectiveness of interventions for the prevention of oral mucositis in cancer patients treated with head and neck radiotherapy and/or chemotherapy, with a focus on randomized clinical trials. A literature search was performed for reports of randomized controlled clinical studies, published between 1966 and 2004, the aim of which was the prevention of mucositis in cancer patients undergoing head and neck radiation, chemotherapy, or chemoradiation. The control group consisted of a placebo, no intervention, or another intervention group. Mucositis was scored by either the WHO, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) score, or the absence or presence of ulcerations, or the presence or absence of grades 3 and 4 mucositis. The meta-analyses included 45 studies fulfilling the inclusion criteria, in which 8 different interventions were evaluated: i.e., local application of chlorhexidine; iseganan; PTA (polymyxin E, tobramycine, and amphotericin B); granulocyte macrophage-colony-stimulating factor/granulocyte colony-stimulating factor (GM-CSF/G-CSF); oral cooling; sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G-CSF. Four interventions showed a significant preventive effect on the development or severity of oral mucositis: PTA with an odds ratio (OR) = 0.61 (95% confidence interval [CI], 0.39–0.96); GM-CSF, OR = 0.53 (CI: 0.33–0.87); oral cooling, OR = 0.3 (CI: 0.16–0.56); and amifostine, OR = 0.37 (CI: 0.15–0.89). To date, no single intervention completely prevents oral mucositis, so combined preventive therapy strategies seem to be required to ensure more successful outcomes.

Predictive modelling for swallowing dysfunction after primary (chemo)radiation: Results of a prospective observational study

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

Detection of unknown primary head and neck tumors by positron emission tomography

The purpose of this study was to investigate the potential of using positron emission tomography (PET) with 18F-labeled fluoro-2-deoxy-D-glucose (FDG) to detect unknown primary tumors of cervical metastases. Thirteen patients with various histologic types of cervical metastases of unknown primary origin were studied. Patients received 185-370 MBq FDG intravenously and were scanned from 30 min after injection onward. Whole-body scans were made with a Siemens ECAT 951/31 PET camera. PET identified the primary tumor in four patients: plasmocytoma, squamous cell carcinoma of the oropharynx, squamous cell carcinoma of the larynx, and bronchial carcinoma, respectively. All known metastatic tumor sites were visualized. PET did not identify a primary tumor in one patient in whom a squamous cell carcinoma at the base of the tongue was found in a later phase. In the remaining eight patients, a primary lesion was never found. The follow up ranged from 18 to 30 months. A previously unknown primary tumor can be identified with FDG-PET in approximately 30% of patients with cervical metastases. PET can reveal useful information that results in more appropriate treatment, and it can be of value in guiding endoscopic biopsies for histologic diagnosis.

Detection of unknown primary tumours and distant metastases in patients with cervical metastases: value of FDG-PET versus conventional modalities

Abstract. In 1%–2% of head and neck oncology patients, the only symptom of a malignancy is a positive cervical node. The aim of this study was to compare the value of positron emission tomography using fluorine-18 fluoro-2-deoxy-D-glucose (FDG-PET) and conventional diagnostic modalities (CT and/or MRI, panendoscopy) in detecting unknown primary tumours and distant metastases in patients suffering from such a cervical metastasis. Fifty patients (37 men and 13 women) with cervical metastases of an unknown primary tumour were included. All patients underwent FDG-PET. In addition, CT and/or MRI was obtained and panendoscopy was performed. All clinically known metastases were detected by FDG-PET. The primary tumour could be diagnosed in 16 patients (four primary tumours were detected exclusively by FDG-PET). Seven patients had multiple distant metastases, that in six cases were detected exclusively by FDG-PET. The sensitivity and specificity of FDG-PET for detection of unknown primary tumours were 100% and 94%, respectively. For the conventional diagnostic modalities these values were 92% and 76%. FDG-PET had an exclusive effect on the applied therapy in 20% of the patients referred for diagnosis of an unknown primary tumour. The data obtained in this study strongly support the diagnostic strategy of performing FDG-PET in patients suffering from cervical metastases of an unknown primary tumour before any other diagnostic technique.

Treatment outcome of bone-anchored craniofacial prostheses after tumor surgery

Percutaneous endosseous implants have acquired an important place in the prosthetic rehabilitation of patients with craniofacial defects. The objective of this study was to evaluate the clinical outcome of the use of endosseous implants in the orbital and auricular region as well as to assess the satisfaction of patients with implant‐retained craniofacial prostheses after tumor surgery.

Morbidity of the neck after head and neck cancer therapy

Studies on morbidity of the neck after head and neck cancer therapy are scarcely described.

18F-FDG PET as a routine posttreatment surveillance tool in oral and oropharyngeal squamous cell carcinoma: a prospective study.

The purpose of this study was to evaluate the role and timing of serial 18F-FDG PET scans as routine surveillance for detecting early locoregional recurrence, distant metastases, and second primary tumors in patients treated for advanced squamous cell carcinoma (SCC) in the oral cavity or oropharynx during the first year after completion of their curative treatment. Methods: Forty-eight consecutive patients with SCC in the oral cavity or oropharynx were included after completing their initial therapy with curative intent. Prospective follow-up of the participants was 2-fold: regular follow-up (history and physical examination) and serial 18F-FDG PET scans. Patients underwent standard follow-up and 18F-FDG PET at 3, 6, 9, and 12 mo after initial treatment. Findings were validated by histopathology or 18 mo of clinical follow-up and imaging after initial treatment. Results: Incidence of recurrences and second primary tumors was 27% and 10%, respectively. 18F-FDG PET was significantly (P = 0.035) more often in agreement with the gold standard than was regular follow-up. 18F-FDG PET showed a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 43%, 51%, and 100%, respectively. For regular follow-up, these values were 0%, 60%, 0%, and 50%, respectively. 18F-FDG PET accounted for a change in diagnostics or treatment in 63% of the patients and regular follow-up in 25% of the patients. Sensitivity and specificity of 18F-FDG PET were both irrespective of timing of 18F-FDG PET. For the 3- and 6-mo posttherapy results combined, 18F-FDG PET detected malignancy in 16 of the 18 patients. Conclusion: 18F-FDG PET is a suitable routine posttreatment surveillance tool in oral and oropharyngeal SCC patients and detects malignancy before clinical suggestion by the regular follow-up arises. The best timing of a systematic 18F-FDG PET scan is between 3 and 6 mo after treatment.

Clinical study for classification of benign, dysplastic, and malignant oral lesions using autofluorescence spectroscopy

Autofluorescence spectroscopy shows promising results for detection and staging of oral (pre-)malignancies. To improve staging reliability, we develop and compare algorithms for lesion classification. Furthermore, we examine the potential for detecting invisible tissue alterations. Autofluorescence spectra are recorded at six excitation wavelengths from 172 benign, dysplastic, and cancerous lesions and from 97 healthy volunteers. We apply principal components analysis (PCA), artificial neural networks, and red/green intensity ratios to separate benign from (pre-)malignant lesions, using four normalization techniques. To assess the potential for detecting invisible tissue alterations, we compare PC scores of healthy mucosa and surroundings/contralateral positions of lesions. The spectra show large variations in shape and intensity within each lesion group. Intensities and PC score distributions demonstrate large overlap between benign and (pre-)malignant lesions. The receiver-operator characteristic areas under the curve (ROC-AUCs) for distinguishing cancerous from healthy tissue are excellent (0.90 to 0.97). However, the ROC-AUCs are too low for classification of benign versus (pre-)malignant mucosa for all methods (0.50 to 0.70). Some statistically significant differences between surrounding/contralateral tissues of benign and healthy tissue and of (pre-)malignant lesions are observed. We can successfully separate healthy mucosa from cancers (ROC-AUC>0.9). However, autofluorescence spectroscopy is not able to distinguish benign from visible (pre-)malignant lesions using our methods (ROC-AUC<0.65). The observed significant differences between healthy tissue and surroundings/contralateral positions of lesions might be useful for invisible tissue alteration detection.