The Summer School Oncology Groningen: Improving a Successful International Course by Refining the Old, Maintaining What's Good.

For more than two decades, the International Summer School Oncology for Medical Students (ISOMS) has organized a biennial 2-week international summer school program in Groningen, the Netherlands. The summer school aims to increase knowledge about general cancer care, reduce fear of talking to cancer patients, and expose students to cancer-related problems. After 22 years, there was a need to improve the summer school format, the application procedure, and the intensity of the course. Here, we describe and evaluate these and additional changes that were made to the program. Several changes were made to the summer school format. The course was shortened from 10 days to a more intensive 7 days. The scientific program was integrated with the clinical program and students were taught scientific writing and presentation skills. The application process involved a personal video pitch. Importantly, the new summer school format was organized by a committee in which medical students had the lead. To evaluate the changes to the summer school, we conducted knowledge tests and regularly obtained feedback. There was a high overall student satisfaction, with a median score of a 9 out of 10. Students appreciated the interactive sessions and practicals and the scientific program, and were satisfied with the course level. All students had improved test scores. Improvement points highlighted the need for a less packed schedule and more lectures on basic oncology principles, or were related to specific lectures. The student-led innovation and adaptation of the ISOMS has been successful.

Coexistence of malnutrition, frailty, physical frailty and disability in patients with COPD starting a pulmonary rehabilitation program.

BACKGROUND & AIMS: Malnutrition, frailty, physical frailty, and disability are common conditions in patients with chronic obstructive pulmonary disease (COPD). Insight in the coexistence and relations between these conditions may provide information on the nature of the relationship between malnutrition and frailty. Such information may help to identify required interventions to improve the patient's health status. We therefore aimed to explore whether malnutrition, frailty, physical frailty, and disability coexist in patients with COPD at the start of pulmonary rehabilitation. METHODS: For this cross-sectional study, from March 2015 to May 2017, patients with COPD were assessed at the start of a pulmonary rehabilitation program. Nutritional status was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA) based Pt-Global app. Frailty was assessed by the Evaluative Frailty Index for Physical activity (EFIP), physical frailty by Fried's criteria, and disability by the Dutch version of World Health Organization Disability Assessment Schedule 2.0 (WHODAS). These variables were dichotomized to determine coexistence of malnutrition, frailty, physical frailty, and disability. Associations between PG-SGA score and respectively EFIP score, Fried's criteria, and WHODAS score were analyzed by Pearson's correlation coefficient. Two tailed P-values were used, and significance was set at P < 0.05. RESULTS: Of the 57 participants included (age 61.2 ± 8.7 years), malnutrition and frailty coexisted in 40%. Malnutrition and physical frailty coexisted in 18%, and malnutrition and disability in 21%. EFIP score and PG-SGA score were significantly correlated (r = 0.43, P = 0.001), as well as Fried's criteria and PG-SGA score (r = 0.37, P = 0.005). CONCLUSIONS: In this population, malnutrition substantially (40%) coexists with frailty. Although the prevalence of each of the four conditions is quite high, the coexistence of all four conditions is limited (11%). The results of our study indicate that nutritional interventions should be delivered by health care professionals across multiple disciplines.

Multi-modality 3D mandibular resection planning in head and neck cancer using CT and MRI data fusion: A clinical series.

OBJECTIVES: 3D virtual surgical planning (VSP) and guided surgery has been proven to be an effective tool for resection and reconstruction of the mandible. Currently, most widely used 3D VSP approaches to mandibular resection do not include detailed tumour information in the VSP. This manuscript presents a strategy where the aim was to incorporate tumour visualisation into the 3D virtual plan. Three-dimensional VSP of the mandibular resections was based on the fusion of CT and MRI data which was subsequently applied in clinical practice. METHODS: All patients diagnosed with oral squamous cell carcinoma between 2014 and 2017 at the University Medical Centre Groningen were included. The tumour was delineated on the MRI data, after which this dataset was fused with the CT bone data in order to construct a 3D bone and tumour model for virtual resection planning. Guided resections were performed and post-operative evaluation quantified the accuracy of the resection. The histopathological findings and patient and tumour characteristics were compared to those of a historical cohort (2009-2014) of conventional mandibular continuity resections. RESULTS: Twenty-four patients were included in the cohort. The average deviation from planned resection was found to be 2.2 mm. Histopathologic analysis confirmed all resection planes (bone) were tumour free, compared to 96.4% in the historic cohort. CONCLUSION: MRI-CT base tumour visualisation and 3D resection planning is a safe and accurate method for oncologic resection of the mandible. It is an improvement on the current methods reported for 3D resection planning based solely on CT data.

High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands.

OBJECTIVES: In cT1-2N0, oral squamous cell carcinoma (OSCC) occult metastases are detected in 23%-37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in head and neck cancer as a minimally invasive alternative for an elective neck dissection in neck staging. Meta-analyses of SLNB accuracy show heterogeneity in the existing studies for reference standards, imaging techniques and pathological examination. The aim of this study was to assess the sensitivity and negative predictive value (NPV) of the SLNB in detecting occult metastases in cT1-2N0 OSCC in a well-defined cohort. DESIGN: Retrospective study. The SLNB procedure consisted of lymphoscintigraphy, SPECT/CT-scanning and gamma probe detection. Routine follow-up was the reference standard for the SLNB negative neck. Histopathological examination of sentinel lymph nodes (SLN) consisted of step serial sectioning, haematoxylin-eosin and cytokeratin AE1/3 staining. SETTING: Two comprehensive oncology centres. PARTICIPANTS: A total of 91 consecutive patients with primary cT1-2N0 OSCC treated by primary resection and neck staging by SLNB procedure between 2008 and 2016. MAIN OUTCOME MEASURES: Sensitivity and negative predictive value. RESULTS: In all cases, SLNs were harvested. A total of 25 (27%) patients had tumour-positive SLNs. The median follow-up was 32 months (range 2-104). Four patients were diagnosed with an isolated regional recurrence in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV. CONCLUSION: In our cohort, the SLNB detected occult metastases in early OSCC with 85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for surgical staging of the neck in case of oral cT1-2N0 SCC.

Evaluation of change in dietitians' perceived comprehensibility and difficulty of the Patient-Generated Subjective Global Assessment (PG-SGA) after a single training in the use of the instrument.

BACKGROUND: The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument used to assess malnutrition and its risk factors. Some items of the PG-SGA may be perceived as hard to comprehend or as difficult by healthcare professionals. The present study aimed to determine whether and how dietitians' perceptions of comprehensibility and difficulty of the PG-SGA change after a single training in PG-SGA use. METHODS: In this prospective evaluation study, Dutch PG-SGA-naïve dietitians completed a questionnaire regarding perceived comprehensibility and difficulty of the PG-SGA before (T0) and after (T1) receiving a single training in the use of the instrument. Perceived comprehensibility and difficulty were operationalised by calculating item and scale indices for comprehensibility (I-CI, S-CI) and difficulty (I-DI, S-DI) at T0 and T1. An item index of 0.78 was considered acceptable, a scale index of 0.80 was considered acceptable and a scale index of 0.90 was considered excellent. RESULTS: A total of 35 participants completed the questionnaire both at T0 and T1. All item indices related to comprehensibility and difficulty improved, although I-DI for the items regarding food intake and physical examination remained below 0.78. Scale indices for difficulty and comprehensibility of the PG-SGA changed significantly (P < 0.001) from not acceptable at T0 (S-CI = 0.69; S-DI = 0.57) to excellent for comprehensibility (S-CI = 0.95) and acceptable for difficulty (S-DI = 0.86) at T1. CONCLUSIONS: The findings of the present study suggest that significant improvement in PG-SGA-naïve dietitians' perception of comprehensibility and difficulty of the PG-SGA can be achieved quickly by providing a 1 day of training in the use of the PG-SGA.

Secondary surgical management of osteoradionecrosis using three-dimensional isodose curve visualization: a report of three cases.

Osteoradionecrosis is defined as bone death secondary to radiotherapy. There is a relationship between the radiation dose received and the occurrence of osteoradionecrosis of the jaws, with the risk increasing above a dose of 60Gy. In cases of class III mandibular osteoradionecrosis, a segmental resection can be indicated. Current practice is to completely remove the affected bone up to the point where the bone looks healthy and is bleeding. Exact resection planning and the use of guided surgery based on imaging of the bone changes have not been reported so far. This article describes a method whereby the radiotherapy dose information is incorporated into the imaging of the affected bone in order to plan a three-dimensional (3D) virtual guided resection and reconstruction of the mandible in osteoradionecrosis. The method enables 3D visualization of each desired dose field in relation to the 3D model of the affected bone. Two types of application - for resection and reconstruction - are described.

Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors.

OBJECTIVE: Salvage surgery has a higher complication rate compared to primary surgical treatment. We evaluated clinical outcome of salvage neck dissections in relation to initial treatment modality, extent of surgery and patient-related factors. DESIGN: Single institution consecutive case series. SETTING: Tertiary Head and Neck Cancer Centre. PARTICIPANTS: In all, 87 patients with head and neck squamous cell carcinoma, who underwent salvage neck dissection after initial radiotherapy (n = 30), radiotherapy with carboplatin/5-fluorouracil (n = 43) or radiotherapy with cetuximab (n = 14). MAIN OUTCOME MEASURES: Incidence of complications, disease-specific survival. RESULTS: Complications occurred in 28% of the patients. Multivariate analysis identified extent of neck dissection as the only independent predictor of surgical complications (P = 0.010). Surgical complication rate was 16% after radiotherapy with systemic treatment, and 47% after radiotherapy alone (P = 0.171). The 5-year disease-specific survival was 55%, independent of complications, initial treatment, extent of surgery and patient-related factors. CONCLUSION: The only predictor for surgical complications was extent of surgery. Survival was not influenced by complications.

RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis.

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC.

Surgery for extra-articular trismus: a systematic review.

The aim of this systematic review was to identify operations that are used to improve mouth opening in patients with extra-articular trismus (caused by cancer and its treatment, oral submucous fibrosis, or noma) and to find out if they work. We searched the electronic databases PubMed, Embase, Cinahl, and the Cochrane collaboration, and then systematically selected papers before we assessed their quality, extracted the data, and did a meta-analysis. We analysed 32 studies that included 651 patients, the median (IQR) size of which was 11 (7-26). The quality of the methods used and of reporting were relatively low. Median (IQR) duration of follow-up was 12 (8-22) months. Operations resulted in a weighted mean (SD) increase in mouth opening of 19.3 (6.3) mm. None of the operations was better than the others for the improvement of mouth opening. We conclude that operations can improve mouth opening in extra-articular trismus, but the evidence is of moderate quality and there is a need for further research.

Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma.

Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed.

Trismus in patients with head and neck cancer: etiopathogenesis, diagnosis and management.

BACKGROUND: Trismus indicates severely restricted mouth opening of any aetiology. A mouth opening of 35 mm or less should be regarded as trismus. Aim of this study was to review the etiopathogenesis, incidence, treatment and prevention of trismus in patients with head and neck cancer. OBJECTIVE OF REVIEW: Trismus is frequently seen in patients suffering from malignant tumours of the head and neck. The reported prevalence of trismus in those patients varies considerably in the literature and ranges from 0 to 100% depending on the tumour site and extension. Trismus may worsen or remain the same over time, or the symptoms may reduce, even in the absence of treatment. When a patient presents with trismus after tumour treatment, it is important to determine whether the trismus is the result of the treatment, or is the first sign of a recurrence. Restricted mouth opening may impede inspection of the oral cavity as needed for dental care, and particularly for oncologic follow-up. CONCLUSIONS: Mouth opening after radiotherapy (RT) decreases on average by approximately 20% compared to mouth opening prior to RT. The prevalence of trismus increases with increasing doses of RT to mastication structures. The use of intensity-modulated RT seems to lower the percentage and severity of RT-induced trismus. Treatment of trismus can be conservative (with either medical or physical therapy) or surgical. Exercise therapy is the mainstay of treatment and exercise should start as soon as possible after treatment. The prevention of trismus, rather than its treatment, is the most important objective.

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye.

BACKGROUND: Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period. METHODS: Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC). RESULTS: Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10-0.47). Only one OSCC was HPV+. CONCLUSIONS: In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.

No evidence for a survival difference between upper and lower lip squamous cell carcinoma.

It is generally assumed that upper lip cancer has a worse survival than lower lip cancer, but this notion is not convincingly supported by limited literature. Therefore, we tested whether upper lip cancer has a worse survival than lower lip cancer. All primary squamous cell carcinoma (SCC) of the lip in the North-East of the Netherlands from 1989-2009 were extracted from the Netherlands Cancer Registry database. We calculated overall and relative survival rates. In this series of 979 lower lip and 126 upper lip SCC, men were 2.6 times more often affected, while the proportionate share of upper lip cancer was larger in women. The 5-year overall survival for lip cancer equaled 74% (95% confidence interval (CI) 70-77%), while the relative survival equaled 97% (95% CI 93-100%). The overall and relative 10-year survival rates were 51% (95% CI 47-54%) and 90% (95% CI 84-96%), respectively. The 10-year relative survival rate for patients with SCC of the upper lip was 94% (95% CI 74-111%) compared to 90% (95% CI 83-96%) for patients with SCC of the lower lip. There appears to be little evidence that patients with upper lip SCC have a worse survival rate.

Mouth opening in patients irradiated for head and neck cancer: a prospective repeated measures study.

OBJECTIVES: Aims of this prospective cohort study were (1) to analyze the course of mouth opening up to 48months post-radiotherapy (RT), (2) to assess risk factors predicting decrease in mouth opening, and (3) to develop a multivariable prediction model for change in mouth opening in a large sample of patients irradiated for head and neck cancer. MATERIALS AND METHODS: Mouth opening was measured prior to RT (baseline) and at 6, 12, 18, 24, 36, and 48months post-RT. The primary outcome variable was mouth opening. Potential risk factors were entered into a linear mixed model analysis (manual backward-stepwise elimination) to create a multivariable prediction model. The interaction terms between time and risk factors that were significantly related to mouth opening were explored. RESULTS: The study population consisted of 641 patients: 70.4% male, mean age at baseline 62.3years (sd 12.5). Primary tumors were predominantly located in the oro- and nasopharynx (25.3%) and oral cavity (20.6%). Mean mouth opening at baseline was 38.7mm (sd 10.8). Six months post-RT, mean mouth opening was smallest, 36.7mm (sd 10.0). In the linear mixed model analysis, mouth opening was statistically predicted by the location of the tumor, natural logarithm of time post-RT in months (Ln (months)), gender, baseline mouth opening, and baseline age. All main effects interacted with Ln (months). CONCLUSION: The mean mouth opening decreased slightly over time. Mouth opening was predicted by tumor location, time, gender, baseline mouth opening, and age. The model can be used to predict mouth opening.

[Three dimensional technology and reconstructions of large defects of the jaw]. / Driedimensionale technologie en reconstructies van grote kaakdefecten.

3D technology is increasingly being applied in dentistry and in oral and maxillofacial surgery. An important field of application is reconstructive surgery, especially in the reconstruction of large defects ofthe jaw. In such cases of reconstruction, the goal is the restoration of both the continuity of the defective area and its function. For the functional restoration implant supported dental structures are often employed. In such cases, CAD/CAM superstructures, 3D printed drill and saw templates, anatomical models, wafers and surgical outcome models are used. The combination of the digital planning and the digital fabrication ofsuperstructures and surgical aids offers many preoperative advantages. The use of saw, drill and positioning templates provides for accurate segmentation and implant positioning, by means of which the reconstruction can be carried out in a predictable way.

Lack of claudin-7 is a strong predictor of regional recurrence in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVES: Adequate treatment of oral and oropharyngeal squamous cell carcinoma (OSCC) is dependent on correctly predicting the presence of lymph node metastases. Current methods to diagnose nodal metastases partly result in overtreatment with associated morbidity and undertreatment with decreased disease-free survival. E-cadherin has been studied extensively as potential marker for lymph node metastases. EpCAM and claudin-7 have a functional relationship with E-cadherin, forming a complex that promotes tumourigenicity in vitro. We hypothesize that the co-expression patterns of these related molecules is a better prognostic marker for nodal status and regional recurrences. MATERIALS AND METHODS: We constructed separate tissue microarrays of tumour centre and tumour invasive front of 227 OSCC with complete clinicopathological and follow-up data, including HPV status, and performed immunohistochemistry for these molecules. RESULTS: Lack of E-cadherin and presence of cytoplasmic EpCAM expression in the tumour front were predictive for nodal metastasis, but no co-expression pattern was found clinically relevant. Lack of claudin-7 in the tumour centre was highly and independently predictive for shorter regional disease-free survival (HR=0.19; 95%CI: 0.06-0.62) and disease-specific survival (HR=0.43; 95%CI: 0.21-0.87). High-risk HPV was not associated with any marker. CONCLUSIONS: The expression of E-cadherin and EpCAM, depending on the specific tumour sublocalization, is predictive for nodal status. However, co-expression did not improve the prediction of nodal status, indicating that the proposed in vitro complex is not functional in clinical samples. Additionally, lack of claudin-7 expression in the tumour centre may be used to identify patients with increased risk for regional recurrence.

FADD expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck.

AIMS: The Fas-associated death domain gene (FADD) is often overexpressed in squamous cell carcinoma of the head and neck (HNSCC), and is considered to be a driver gene in amplification of the chromosomal 11q13.3 region. Amplification of 11q13.3 is associated with increased metastasis in HNSCC and breast cancer. The aim of this study was to investigate the association between FADD protein expression in advanced-stage HNSCC and clinicopathological features and outcome. METHODS AND RESULTS: Tumour tissues of 177 HNSCC patients uniformly treated with primary surgery and postoperative radiotherapy were collected. FADD expression was assessed on pretreatment tumour biopsies using immunohistochemistry. High FADD expression was detected in 44% of the HNSCC patients. High expression was associated with an increased rate of lymph node metastasis (P = 0.001) and with a shorter distant metastasis-free interval (DMFI) (HR 2.6, 95% CI 1.0-6.7, P = 0.046) when lymph node metastases were present. CONCLUSIONS: Our data show that an increase in FADD expression is associated with a higher incidence of lymph node metastasis at presentation, and with shorter DMFI when lymph node metastases are present. High FADD expression in the primary tumour could be a useful marker to select patients for systemic treatment strategies that reduce the risk of distant metastases.

mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck: a systematic review.

OBJECTIVE: Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC). To evaluate available evidence on the use of mTHPC (Foscan®) mediated PDT, we conducted a review of the literature. MATERIALS AND METHODS: A systematic review was performed by searching seven bibliographic databases on database specific mesh terms and free text words in the categories; "head and neck neoplasms", "Photodynamic Therapy" and "Foscan". Papers identified were assessed on several criteria by two independent reviewers. RESULTS: The search identified 566 unique papers. Twelve studies were included for our review. Six studies reported PDT with curative intent and six studies reported PDT with palliative intent, of which three studies used interstitial PDT. The studies did not compare PDT to other treatments and none exceeded level 3 using the Oxford levels of evidence. Pooling of data (n=301) was possible for four of the six studies with curative intent. T1 tumors showed higher complete response rates compared to T2 (86% vs 63%). PDT with palliative intent was predominantly used in patients unsuitable for further conventional treatment. After PDT, substantial tumor response and increase in quality of life was observed. Complications of PDT were mostly related to non-compliance to light restriction guidelines. CONCLUSION: The studies on mTHPC mediated PDT for HNSCC are not sufficient for adequate assessment of the efficacy for curative intent. To assess efficacy of PDT with curative intent, high quality comparative, randomized studies are needed. Palliative treatment with PDT seems to increase the quality of life in otherwise untreatable patients.