External beam radiotherapy with endocavitary boost for nasopharyngeal cancer: treatment results and late toxicity after extended follow-up.

PURPOSE: To evaluate the long-term outcome after treatment of nasopharyngeal carcinoma and assess late toxicity in a multidisciplinary clinic. METHODS AND MATERIALS: A retrospective analysis of 117 patients treated for nasopharyngeal cancer in a single institute between 1985 and 2002 was performed. Fifty-one long-term survivors were evaluated for late toxicity by a multidisciplinary team comprising a radiation oncologist, otolaryngologist, neurologist, and oral and maxillofacial surgeon. RESULTS: The 5-year local control rate for T1 to T2 and T3 to T4 tumors was 97% and 76%, respectively. Five-year disease-free survival and overall survival were 82% and 88% for Stage I to IIb disease and 46% and 52% for Stage III to IVb, respectively. Late morbidity evaluation revealed Radiation Therapy Oncology Group (RTOG) Grade III to IV toxicity in 71% of patients. A high incidence of cranial nerve palsies (47%) and mandibular osteolysis (82%) was found, although these complications had limited clinical impact. CONCLUSIONS: The multidisciplinary late morbidity clinic revealed an unexpected high incidence of cranial nerve palsies and mandibular osteolysis and overall an RTOG Grade III to IV toxicity in 71% of patients treated for nasopharyngeal cancer. External beam radiotherapy with endocavitary brachytherapy produces excellent rates of local control for T1 to T2 tumors, but the high incidence of late toxicity suggests an overtreatment.

Can FDG-PET assist in radiotherapy target volume definition of metastatic lymph nodes in head-and-neck cancer?

BACKGROUND AND PURPOSE: The role of FDG-PET in radiotherapy target volume definition of the neck was evaluated by comparing eight methods of FDG-PET segmentation to the current CT-based practice of lymph node assessment in head-and-neck cancer patients. MATERIALS AND METHODS: Seventy-eight head-and-neck cancer patients underwent coregistered CT- and FDG-PET scans. Lymph nodes were classified as "enlarged" if the shortest axial diameter on CT was 10mm, and as "marginally enlarged" if it was 7-10mm. Subsequently, lymph nodes were assessed on FDG-PET applying eight segmentation methods: visual interpretation (PET(VIS)), applying fixed thresholds at a standardized uptake value (SUV) of 2.5 and at 40% and 50% of the maximum signal intensity of the primary tumor (PET(SUV), PET(40%), PET(50%)) and applying a variable threshold based on the signal-to-background ratio (PET(SBR)). Finally, PET(40%N), PET(50%N) and PET(SBRN) were acquired using the signal of the lymph node as the threshold reference. RESULTS: Of 108 nodes classified as "enlarged" on CT, 75% were also identified by PET(VIS), 59% by PET(40%), 43% by PET(50%) and 43% by PET(SBR). Of 100 nodes classified as "marginally enlarged", only a minority were visualized by FDG-PET. The respective numbers were 26%, 10%, 7% and 8% for PET(VIS), PET(40%), PET(50%) and PET(SBR). PET(40%N), PET(50%N) and PET(SBRN), respectively, identified 66%, 82% and 96% of the PET(VIS)-positive nodes. CONCLUSIONS: Many lymph nodes that are enlarged and considered metastatic by standard CT-based criteria appear to be negative on FDG-PET scan. Alternately, a small proportion of marginally enlarged nodes are positive on FDG-PET scan. However, the results are largely dependent on the PET segmentation tool used, and until proper validation FDG-PET is not recommended for target volume definition of metastatic lymph nodes in routine practice.

QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries.

OBJECTIVE: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. METHODS: The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. RESULTS: Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 50% of patients had high disease activity of DAS28 >5.1. CONCLUSIONS: This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.

Are glucocorticoids DMARDs?

Disease modifying antirheumatic drugs (DMARDs) are drugs used in rheumatoid arthritis (RA) to control the disease and to limit joint damage and improve long-term outcome. The last decade evidence has accumulated that suggests that low dosages of glucocorticoids are indeed able to control the disease and limit the destruction. This role is especially present in early disease and in combination with other drugs. The evidence is carefully evaluated and discussed. The ultimate conclusion is that indeed glucocorticoids are DMARDs and are especially useful in early RA.

Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo.

OBJECTIVE: In a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial. METHODS: A blinded assessment of radiographic joint damage was performed approximately 3 years after the end of the original 2-year study. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. RESULTS: During 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period. CONCLUSION: The inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.

Five-year followup of rheumatoid arthritis patients after early treatment with disease-modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year.

OBJECTIVE: To evaluate whether the clinical advantages observed after 1 year in a randomized controlled clinical trial, in which 2 treatment strategies were compared (the early disease-modifying antirheumatic drug [DMARD] approach versus the pyramid approach), persist after 5 years. METHODS: In this study, 238 patients with recently diagnosed rheumatoid arthritis (RA) were randomized to either the pyramid group (n = 56) or the early DMARD group (n = 182). Patients assigned to the pyramid group received nonsteroidal antiinflammatory drugs for at least 1 year after inclusion (the mean +/- SD lag time until first prescription of a DMARD was 14 +/- 9 months). Patients in the early DMARD group were treated with a DMARD immediately after inclusion. RESULTS: After 5 years, data were available for 44 patients in the pyramid group (79%) and 145 patients in the early DMARD group (80%). No prolongation of the clinical advantages in favor of the early DMARD group, as observed after the first year, was demonstrated. Nevertheless, a significantly shorter delay time until complete response and a higher number of patients with overall clinically relevant improvement at several assessment points were observed in the early DMARD group compared with the pyramid group. CONCLUSION: The clinical results in favor of the early DMARD group, as observed after the first year, were not as evident after 5 years. This indicates that a more aggressive treatment approach in early RA is required, and that treatment should be continued for a prolonged period of time, in order to maintain the advantages obtained in the first year.