Success rate of thyroid remnant ablation for differentiated thyroid cancer based on 5550 MBq post-therapy scan.

BACKGROUND: Success rate of thyroid remnant ablation in patients with low-risk differentiated thyroid cancer (DTC) is commonly based on measurement of serum thyroglobulin levels and 185 MBq (5 mCi) diagnostic 131I scanning or neck ultrasound, performed 6-9 months after ablation. In the present study, we report the rates of successful 131I ablation based on a 5550 MBq (150 mCi) post-therapy scan performed 6-9 months after ablation. METHODS: Retrospective cohort study of 77 adult patients with DTC, stage T1-T3, N0 or N1, M0, demonstrating thyroid remnant uptake one week after a 2775 MBq (75 mCi) ablation dose. Six to nine months later, all patients received a 5550 MBq dose of 131I, followed by a post- therapy scan after one week. Complete thyroid ablation was defined as no thyroid remnant uptake and a thyroglobulin level < 0.2 µg/l after thyroid hormone withdrawal. RESULTS: Thyroid ablation was complete in 20 patients (26%). Forty-eight patients (62%) demonstrated persistent remnant uptake. This was associated with thyroglobulin levels > 0.2 µg/l in 24/48, and positive thyroglobulin antibodies in 4/48 patients. CONCLUSION: Thyroid remnant ablation success assessed by 5550 MBq post-therapy scanning was much lower than reported in studies evaluating ablation success based on 185 MBq diagnostic 131I scanning or neck ultrasound. The latter techniques may be too inaccurate to detect thyroid remnants and thus may not be sufficiently reliable to predict long-term disease outcome.

[18 FDG PET imaging of the brain in the analysis of a dementia syndrome]. / De rol van de 18-fDG PET-scan bij de diagnose dementie.

According to current dementia guidelines from 2005 (CBO) functional brain imaging by PET-scan of the brain has no place in the analysis of a dementia syndrome. Differential diagnosis between Alzheimer disease and other causes of dementia remains important because there are differences in natural course and treatment. Here we present three patients aged 62, 71 and 68 years with dementia syndrome who were assessed at an outpatient memory clinic. After geriatric assessment and subsequent brain MRI the etiology of the dementia remained unclear. In all three patients the etiology became clear after using a 18 FDG PET-scan of the brain. We conclude that 18 FDG PET imaging of the brain has added value in the analysis of dementia syndrome with an unclear etiology after initial analysis.

The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer.

BACKGROUND: Sentinel node biopsy is a standard diagnostic component for the treatment of patients with a primary mammary carcinoma. By concomitantly performing intraoperative lymph node biopsy and primary tumor resection, patients with a positive sentinel node (SN) are not subjected to the inconvenience and risks of second surgical intervention. The aim of this retrospective study was to determine the sensitivity, accuracy and long-term consequences of the frozen section (FS) examination of the SN in breast cancer patients. METHODS: Sentinel lymph node biopsy was performed in 615 patients with an invasive tumor of the breast. Frozen sections of the SN were taken from the optimal cross-sectional surface. Serial sections were made from the remaining SN and stained using hematoxylin-eosin and immunohistochemistry. RESULTS: Sentinel node frozen biopsy accurately predicted the state of the axilla in 559 (90.7%) patients. There were 50 false-negative findings in patients with sentinel node metastases. The sensitivity and specificity of the intraoperative frozen section examination were 71.6% and 100%, respectively. Follow-up (mean 36.3 months) of all false-negative cases showed no development of local axillary recurrence. The results demonstrated no significant relation between tumor size and frozen section sensitivity. Frozen section investigation was less sensitive in ascertaining micrometastases (sensitivity 61.1%) than macrometastases (sensitivity 84.0%, p<0.001). CONCLUSION: Intraoperative frozen section examination of the sentinel node is a useful predictor of axillary lymph node status in breast cancer patients. Seventy-two percent of the patients with metastatic disease were correctly diagnosed and spared a second surgical procedure.

High-T(c) superconducting thin films with composition control on a sub-unit cell level; the effect of the polar nature of the cuprates.

Inspired by the work of Ohtomo and Hwang in 2004, we shed new light on thin films of layered cuprate high-T(c) superconductors (HTS). In principle all HTS materials consist of charged perovskite-like layers which in thin films can lead to polar discontinuities at the interfaces of different materials. The resulting charge redistribution has to occur but we expect it to be far more complex than in the LaAlO(3)/SrTiO(3) system since copper can be multivalent. This makes it hard to predict what will happen in terms of transport or even magnetic properties compared to the 'simple' insulator LaAlO(3). Nevertheless, we point out that the picture of systems of charged layers is important and necessary to fully understand heterostructures of these complex materials.

[Results from a general training hospital for the implementation of a diagnostic workup for pulmonary embolism according to the Dutch Institute for Health Care Improvement]. / Resultaten van het invoeren van diagnostiek naar longembolie volgens de CBO-richtlijn in een algemeen opleidingsziekenhuis.

OBJECTIVE: To evaluate the active implementation of the Dutch Institute for Healthcare Improvement's guideline for the diagnostic work-up for pulmonary embolism in a general training hospital, and to analyse reasons for not following the guideline strategy. DESIGN: Partly retrospective and partly prospective. METHOD: The diagnostic strategy was analysed for all consecutive patients with clinically suspected pulmonary embolism who underwent a perfusion lung scintigraphy. The extent to which the guideline was followed was investigated in the year before (July 1999-June 2000; n = 384) and the year after (July 2000-June 2001; n = 380) its active implementation. The possible reasons for not completing the strategy in the prospective cohort of the study were also analysed. RESULTS: Following a non-high-probability perfusion-ventilation scan, the guideline was completed in 23/117 (20%) patients prior to the implementation and in 50/109 (46%) patients after the implementation of the guideline. In 27% and 60%, respectively, an additional duplex ultrasound of the legs was made to check for deep vein thrombosis, and in 65% and 70% respectively, pulmonary angiography was performed after a normal ultrasound result. The main reasons for not following the diagnostic work-up included low clinical probability (41%, without a proper alternative diagnosis), an alternative diagnosis (36%; pneumonia, heart failure, malignancy) and a reluctance to perform angiography. The mean age of the patients for whom the guideline was completed was lower (51 years) compared to patients for whom the guideline was not followed (65 years; p < 0.001). The risk of not completing the diagnostic workup in accordance with the guideline was six-fold higher for patients > or = 80 years compared with patients < 40 years of age, whereas an alternative diagnosis was not more prevalent in patients > or = 65 years. CONCLUSION: Although active implementation of the guideline-based diagnostic work-up for pulmonary embolism increased the number of adequate diagnoses, the diagnostic work-up was not completed in half of the patients with inconclusive lung scans. The main reasons for this were the advanced age of the patient, alternative diagnoses, and a reluctance to perform pulmonary angiography.

Determination of the accuracy of implant reconstruction and dose delivery in brachytherapy in The Netherlands and Belgium.

PURPOSE: To gain insight into the accuracy of brachytherapy treatments, the accuracy of implant reconstruction and dose delivery was investigated in 33 radiotherapy institutions in The Netherlands and Belgium. MATERIALS AND METHODS: The accuracy of the implant reconstruction method was determined using a cubic phantom containing 25 spheres at well-known positions. Reconstruction measurements were obtained on 41 brachytherapy localizers, 33 of which were simulators. The reconstructed distances between the spheres were compared with the true distances. The accuracy of the dose delivery was determined for high dose rate (HDR), pulsed dose rate (PDR) and low dose rate (LDR) afterloading systems using a polymethyl methacrylate cylindrical phantom containing a NE 2571 ionization chamber in its centre. The institutions were asked to deliver a prescribed dose at the centre of the phantom. The measured dose was compared with the prescribed dose. RESULTS: The average reconstruction accuracy was -0.07 mm (+/-0.4 mm, 1 SD) for 41 localizers. The average deviation of the measured dose from the prescribed dose was +0.9% (+/-1.3%, 1 SD) for 21 HDR afterloading systems, +1.0% (+/-2.3%, 1 SD) for 12 PDR afterloaders, and +1.8% (+/-2.5%, 1 SD) for 15 LDR afterloaders. CONCLUSIONS: This comparison showed a good accuracy of brachytherapy implant reconstruction and dose delivery in The Netherlands and Belgium.

The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment.

PURPOSE: To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were reviewed. After redigitizing the films, primary and nodal tumor volume was calculated with the summation-of-areas technique. The nodal CT aspect was graded using a 3-point scale (homogenous, inhomogeneous, and necrotic). Mean follow-up time was 33 months. Actuarial statistical analysis of local and regional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis, CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.05) when all patients were considered, but primary tumor volume did not predict local control within the T2, T3, and T4 category. CT-determined nodal volume was significantly related to regional outcome (p < 0.01), but nodal density was not. Total tumor volume was not significantly related to locoregional outcome (p = 0.1). In the multivariate analysis, the T and N categories were the independent predictors of local and regional outcomes, respectively. CONCLUSION: Compared to other head-and-neck sites, primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer.

Radiotherapy for PSA recurrence after radical prostatectomy.

OBJECTIVES: The treatment of patients presenting with an isolated PSA recurrence after radical prostatectomy (RP) remains controversial. The present study aims at assessing the results of salvage radiotherapy (RT), to define prognostic factors and to identify subgroups of patients most suitable for RT with curative intent. MATERIALS AND METHODS: A retrospective study was performed of 53 patients, diagnosed with a rising PSA after RP, and treated with RT to the prostate bed, between July 1992 and July 1998. RESULTS: On univariate analysis, significant determinants to obtain and maintain a nondetectable PSA (< 0.02 ng/ml) were Gleason grade (< or = III vs. < or = IV), pre-RT PSA, considered as categorical or continuous variable, and pathological stage, pT (2 vs. 3). Pre-RP PSA (< or = 10 vs. >10), time interval between surgery and moment of rising PSA and pathological section margin status were not significant. On multivariate analysis, only Gleason grade and pre-RT PSA remained significant. For the patient group with a Gleason grade < or = III the PSA-free survival at 3 years was 75% (+/- 11%) compared to 27% (+/- 9%) for the patients with a Gleason grade > or = IV (p = 0.002). Pre-RT PSA significantly influenced PSA-free survival in the first group, but not in the latter. CONCLUSION: From the group of RP patients with rising PSA following a postsurgery PSA-free period, subgroups can be defined with a distinctly different probability of obtaining and maintaining nondetectable PSA levels after salvage RT.

The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy.

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.

Improvement of Clostridium tumour targeting vectors evaluated in rat rhabdomyosarcomas.

Previous studies have demonstrated the feasibility of using apathogenic clostridia as a promising strategy for hypoxia-specific tumour targeting. The present study shows that the use of the vascular targeting compound combretastatin A-4 phosphate could significantly (P<0.001) increase the number of Clostridium vegetative cells in rat rhabdomyosarcomas with sizes between 0.2 cm(2) and 3 cm(2). Furthermore, this study showed that administration of metronidazole for a 9-day period was sufficient to eliminate systemically administered Clostridium from the tumour. Moreover, previous Clostridium spore administration did not effect tumour colonisation, regardless of the immune response status of the host.

In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment.

PURPOSE: Interference with the tumor blood vessels through anti-angiogenesis or vascular targeting can indirectly suppress tumor growth. Vascular targeting of solid tumors, using tubulin-compromising agents, seems a promising and selective novel treatment. We aimed to evaluate the potential (hypothesis-based) benefit from combinations of vascular targeting using combretastatin A-4 phosphate (combreAp) with either ionizing radiation or anti-angiogenesis. METHODS AND MATERIALS: Rhabdomyosarcoma tumor pieces were inplanted subcutaneously (s.c.) in the lower flank region of syngeneic adult WAG/Rij rats. Tumors were grown until different sizes and stratified for the various treatment groups: small (1-3 cm3), medium (3.1-7 cm3), and large (7.1-14 cm3). CombreAp was injected i.p.; injections of TNP-470 were s.c. in the neck area. Localized single-dose (8 Gy) irradiations of tumors were done under Nembutal anesthesia, always 1 day before a single combreAp (25 mg/kg) injection. The TNP-470 treatment (3 times 30 mg/kg in 1 week) started 1 day after a double (8 days interval between both) combreAp administration. Tumor responses were evaluated by the growth delay assay, and statistical significance of tumor growth change was computed. RESULTS: Large tumors responded better to combreAp treatment given alone than did the smaller ones, confirming our previous data with this tumor model. Combining irradiation with combreAp also resulted in a tumor size-dependent growth delay. With small and medium tumor volumes, a similar response was measured after the combination treatment when compared with irradiation only. Large tumors, however, showed a strong (at least additive) increase of the growth delay with the combined therapy; the difference in tumor growth between the two treatment groups was very significant (p < 0.0001). m When TNP-470 was combined with combreAp, no significant lengthening of the growth delay, irrespective of the tumor size, was present with the applied schedule. CONCLUSION: The current data show a significant advantage in the combination of combreAp with irradiation in rhabdomyosarcomas having a large size (7-14 cm3) at treatment. Such a benefit in tumor response was not observed with the smaller tumors, seemingly because irradiation as such was very effective. No significant gain in growth delay for any tumor size was observed when TNP-470, showing efficacy on its own specifically with tumors measuring <7 cm3, was added to the combreAp treatment. This presumably reflects only little angiogenesis during the first week of rhabdomyosarcoma regrowth after the combreAp treatment.

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

BACKGROUND AND PURPOSE: In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. MATERIALS AND METHODS: Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. RESULTS: The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). CONCLUSION: Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Palliative radiotherapy practice within Western European countries: impact of the radiotherapy financing system?

PURPOSE: To analyze the reimbursement modalities for radiotherapy in the different Western European countries, as well as to investigate if these differences have an impact on the palliative radiotherapy practice for bone metastases. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres included in the 1997 ESTRO directory. In this questionnaire the reimbursement strategy applied in the different centres was assessed, with respect to the use of a budget (departmental or hospital budget), case payment and/or fee-for-service reimbursement. The differences were analyzed according to country and to type and size of the radiotherapy centre. RESULTS: A total of 170 centres (86% of the responders) returned the questionnaire. Most frequent is budget reimbursement: some form of budget reimbursement is found in 69% of the centres, whereas 46% of the centres are partly reimbursed through fee-for-service and 35% through case payment. The larger the department, the more frequent the reimbursement through a budget or a case payment system and the less the importance of fee-for-service reimbursement (chi(2): P=0.0012; logit: P=0.0055). Whereas private centres are almost equally reimbursed by fee-for-service financing as by budget or case payment, radiotherapy departments in university hospitals receive the largest part of their financial resources through a budget or by case payment (83%) (chi(2): P=0.002; logit: P=0.0073). A correlation between the country and the radiotherapy reimbursement system was also demonstrated (P=0.002), radiotherapy centres in Spain, the Netherlands and the United Kingdom being almost entirely reimbursed through a budget and/or case payment and centres in Germany and Switzerland mostly through a fee-for-service system. In budget and case payment financing lower total number of fractions and lower total dose (chi(2): P=0.003; logit: P=0.0120) as well as less shielding blocks (chi(2): P=0.003; logit: P=0.0066) are used. A same tendency is found for the use of isodose calculations and field set-up, but without being statistically significant (P=0.264 and P=0.061 res.). The type of the centre and the reimbursement modality influence the fractionation regimen independently (P=0.0274). This is not the case for the centre size and the reimbursement, which were found to exert correlated effects on the fractionation schedule (P=0.1042). CONCLUSION: Reimbursement systems seem to influence radiotherapy practice. One should therefore aim to develop reimbursement criteria that pursue to deliver, not only the best qualitative, but also the most cost-effective treatments to the patients.

Differences in palliative radiotherapy for bone metastases within Western European countries.

PURPOSE: To evaluate the differences in palliative radiotherapy for painful bone metastases amongst different Western European countries. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres in 19 Western European countries, based on the 1997 ESTRO directory. In this questionnaire the current local palliative radiotherapy practice for bone metastases was assessed in terms of total dose, fractionation, treatment complexity (use of shielding blocks, frequency of isodose calculations, field set-up) and type of machine used. The differences were analyzed according to the country and to the type and size of radiotherapy centre. RESULTS: A total of 205 centres (36%) returned the questionnaire, of which 198 could be further analyzed. The most frequently used antalgic fractionation schedule is 30 Gy in ten daily fractions of 3 Gy (50%), single fractions and conventional 2 Gy fractions being used in a minority of the centres (respectively, 11 and 9%). Most antalgic treatments are performed on a linear accelerator (67% of the centres uses linear accelerators) and 64% of the centres predominantly uses a two-field set-up. The majority of the centres uses shielding blocks and performs isodose calculations in less than 50% of the patients, (respectively, 88 and 81%). There is a correlation between the centre size and the palliative irradiation practice, the largest centres using more hypofractionation (chi(2): P=0.001; logit: P=0. 0003) and a less complex treatment set up as expressed by the use of isodose calculations (chi(2): P=0.027; logit: P=0.0161). There is also a tendency to use less shielding blocks (P=0.177). The same goes for university centres as compared with private centres: university centres use shorter fractionation schedules (chi(2): P=0. 008; logit: P=0.0094), less isodoses (chi(2): P=0.010; logit: P=0. 0115) and somewhat less shielding blocks (P=0.151). Amongst the analyzed countries different tendencies in fractionation (P=0.001) and treatment complexity are observed (use of isodoses: P=0.014, use of shielding blocks: P=0.001). CONCLUSION: These data suggest that beside work-load and clinical evidence, country-related factors such as tradition and habits, past teaching, the national organization of health care and reimbursement criteria may influence the local practice.

Human cartilage gp-39+,CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis.

OBJECTIVE: To investigate the expression of human cartilage (HC) gp-39, a possible autoantigen in rheumatoid arthritis (RA), in peripheral blood and synovium, to characterize its cellular source, and to analyze correlations with clinical features. METHODS: The expression of HC gp-39 in synovium and peripheral blood mononuclear cells (PBMC) was assessed by immunohistochemistry and flow cytometry. Synthesis and secretion were investigated by both reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: PBMC expressing HC gp-39 were increased in RA patients compared with spondylarthropathy patients (P = 0.0029) and with healthy control subjects (P = 0.0013). HC gp-39+ cells were also slightly overrepresented in RA synovium (P = 0.01). In both blood and synovium, HC gp-39+ cells were identified as CD14dim,CD16+ monocytes, a phenotype which can differentiate from classic CD14++ monocytes by maturation in vitro. HC gp-39 messenger RNA was detected in RA synovium and PBMC, and PBMC secreted HC gp-39 in vitro. The number of HC gp-39+ PBMC correlated with serum levels of C-reactive protein (r = 0.39, P = 0.003) and HC gp-39 (r = 0.52, P = 0.014). HC gp-39 expression in RA synovial lining correlated with joint destruction (r = 0.77, P < 0.001). CONCLUSION: CD16+ monocytes, a cellular source of HC gp-39 in vivo, are overrepresented in both RA peripheral blood and synovial tissue. The presence of HC gp-39+ cells in RA synovium is correlated with the degree of joint destruction. These data support a role of these cells in the local autoimmune response that leads to chronic inflammation and joint destruction.

Long term survival of a patient with malignant pleural mesothelioma as a late complication of radiotherapy for Hodgkin's disease treated with 90yttrium-silicate.

A case of malignant pleural mesothelioma (PM) 24 years after thoracic radiotherapy for Hodgkin's disease is presented. As primary treatment and to relieve symptoms of dyspnea secondary to pleural effusion a thoracic drain was installed, followed by intracavitary radiation therapy with 90yttrium-silicate. Minor complaints of fever and a dry cough as a side-effect of this treatment were effectively treated with prednisone during 2 weeks. The patient remains in a good clinical condition now 6 years after diagnosis. Considering the few therapeutic options the use of 90yttrium-silicate intrapleural installation could be propagated as a safe and effective antitumour treatment for a selected group of patients with malignant PM.

Value of computed tomography as outcome predictor of supraglottic squamous cell carcinoma treated by definitive radiation therapy.

PURPOSE: To investigate the value of several CT-derived tumor parameters as predictors of local outcome of supraglottic squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 103 patients with supraglottic squamous cell carcinoma were reviewed for tumoral involvement of specific laryngeal anatomic subsites and extralaryngeal tumor spread. After redigitizing the films, tumor volume was calculated with the summation-of-areas technique. Mean follow-up time was 3.4 years. Actuarial statistical analysis of local and locoregional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.001). Degree of involvement of the paraglottic space at the level of the true vocal cord (p < 0.05) and subglottic extension (p < 0.001) were also significantly correlated with local recurrence rate. In the multivariate analysis, only degree of involvement of the preepiglottic space (p < 0.01) and subglottic extension (p < 0.01) were found to be independent predictors of local recurrence. Total tumor volume was the strongest independent predictor of locoregional failure (p < 0.01). CONCLUSIONS: CT-determined tumor parameters are strong predictors of local and locoregional outcome of supraglottic carcinoma treated by definitive irradiation.

T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles.

OBJECTIVE: To analyze the CD4+ T cell responses to the human cartilage antigen glycoprotein-39 (HCgp-39) in the context of rheumatoid arthritis (RA)-associated (DRalphabeta1*0401) and nonassociated (DRalphabeta1*0402) HLA class II molecules. METHODS: Large numbers of HCgp-39-specific T cell hybridomas were generated following immunization of HLA-DR4/human CD4 transgenic, murine major histocompatibility complex class II deficient mice with native HCgp-39. Fine epitope mapping of DRalphabeta1*0401-and DRalphabeta1*0402-restricted T cell hybridomas was performed using overlapping synthetic peptides. Antigen-specific cytokine production by lymph node T cells was evaluated after immunization with native antigen. Proliferative T cell responses of healthy human subjects were compared with the T cell responses of patients with active RA using HCgp-39 epitopes defined in HLA-DR4 transgenic mice. RESULTS: CD4+ T cells from DRalphabeta1*0401 and DRalphabeta1*0402 transgenic mice identified completely different immunodominant peptide epitopes of HCgp-39, and this was not explained by known DR4-binding motifs or direct peptide-binding studies. DRalphabeta1*0401-restricted, antigen-specific T cells produced significantly more interferon-gamma and tumor necrosis factor a in response to HCgp-39 than did T cells from DRalphabeta1*0402 transgenic mice. Finally, HCgp-39 peptides defined in DRalphabeta1*0401 transgenic mice stimulated T cells from HLA-DR4 positive human subjects and RA patients, but not T cells from HLA-DR4 negative individuals. CONCLUSION: T cell epitopes of HCgp-39 that were defined in HLA-DR4 transgenic mice stimulated T cells from human subjects carrying RA-associated HLA-DR4 alleles. HLA-DR4 molecules may influence the disease process in RA both by presentation of selected peptide epitopes and by promoting the production of proinflammatory cytokines in synovial joints.