Evidence-based recommendations on the role of dermatologists in the diagnosis and management of psoriatic arthritis: systematic review and expert opinion.

BACKGROUND: Psoriatic arthritis (PsA) can develop at any time during the course of psoriasis. AIMS: The aims of these practical recommendations are to help dermatologists identify patients at risk of PsA, to diagnose PsA in collaboration with rheumatologists and to gain a better understanding of initial PsA management. MATERIALS AND METHODS: A scientific committee consisting of 10 dermatologists and a rheumatologist selected clinically relevant questions to be addressed by evidence-based recommendations using the DELPHI method. For each question, a systematic literature review was performed in Medline, Embase and the Cochrane Library databases. The levels of evidence of all selected and reviewed articles were appraised according to the Oxford levels of evidence. RESULTS: An expert board of 30 dermatologists reviewed and analysed the evidence and developed recommendations for the selected questions. Agreement among participants was assessed on a 10-point scale, and the potential impact of the recommendations on clinical practice was evaluated. Among the 6960 references identified, 190 relevant articles were included in the reviews. Three recommendations regarding risk factors for PsA and one regarding PsA prevalence were issued. The mean agreement score between participants varied from 7.8 to 9.6. Three recommendations on PsA screening tools that can be used by dermatologists were issued. The mean agreement score between participants varied from 7.7 to 9.4. Initial PsA treatment options according to published guidelines were critically appraised for axial and peripheral involvement and enthesitis/dactylitis. Three recommendations were issued. The mean agreement score between participants varied from 7.6 to 8.7. DISCUSSION: The systematic literature research and meta-analyses did not provide high-quality evidence to support recommendations regarding PsA screening. Conversely, PsA treatment options were supported by strong evidence. CONCLUSION: Cooperation between dermatologists and rheumatologists should be emphasized to better identify and manage PsA patients.

Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion.

BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis whose the association with psoriatic arthritis (PsA) has been recently described. There is limited evidence regarding how to best reduce palmoplantar pustular psoriasis severity and to maintain remission once achieved. OBJECTIVE: The aim of this study was to elaborate evidence-based recommendations for PPPP treatment supported by a systematic literature review. METHODS: A systematic literature search was carried out in Embase, Medline and Cochrane Library databases from 1980 to February 2013 searching for any trial in patients with PPPP assessing therapeutic interventions not including a systemic biotherapy. The selection of articles was limited to human subjects and English or French languages. RESULTS: Among the 675 articles identified, 29 including one Cochrane review were analysed. The Cochrane review summarised 23 randomised controlled trials (RCTs) in chronic PPPP until February 2003, including 724 patients. The authors concluded that oral retinoid therapy (acitretin), photochemotherapy or combination of both, low dose of ciclosporin or topical corticosteroids under occlusion appeared to be helpful in relieving symptoms of PPPP. Since the publication of this review, 9 open studies on PPPP treatment have been published. Three new studies evaluated the benefits of PUVA on PPPP. They all showed a better efficacy of PUVA compared to UVB therapy. One open study concluded that a retinoid treatment with an arotinoid ethylesther showed a good efficacy. Five prospective studies (level of evidence of 3) assessed Laser Excimer UVB-NB (Excimer 308 nm) in PPPP. The combined analysis of these studies showed that 64% of patients experienced an improvement of 70% at the end of treatment. CONCLUSION: Phototherapy, ciclosporin and topical corticosteroids seem to be able to control PPPP. However, the standard of care for PPPP remains an issue and there is a strong need for reliable RCTs to better define treatment strategies for PPPP.

Is there a psoriasis skin phenotype associated with psoriatic arthritis? Systematic literature review.

Psoriatic arthritis (PsA) is associated with psoriasis with a prevalence varying from 5.94% to 23.9%. The aim of this study was to assess if some psoriatic skin features are associated with a higher risk of PsA. A systematic literature search was carried out from 1980 to January 2013, in the Embase and Pubmed databases, using a combination of keywords including (Psoriasis) AND (PsA). Of the 2746 articles retrieved, 25 references were selected. Meta-analysis was performed when possible. Mean age at psoriasis onset appeared to be similar among patients with skin disease alone and in those with PsA. There was no clinical type of psoriasis specifically associated with PsA, including pustular psoriasis of palms and soles. Nonetheless specific psoriasis localizations were significantly associated with an increased risk of developing PsA in one cohort study: scalp lesions [Hazard Ratio (HR) 3.89 (95% confidence interval (CI):2.18-6.94)] and intergluteal/perianal lesions [HR 2.35 (95%CI:1.32-4.19)]. A similar association was found in two cross-sectional studies. Nail involvement was significantly associated with PsA in the meta-analysis [Odds Ratio (OR) 2.92 (95% CI 2.34-3.64)], particularly onycholysis [OR 2.38 (95% CI 1.74-3.26)]. Moreover, nail psoriasis was also associated with distal interphalangeal joint arthritis. The extent of psoriasis appeared to be associated with PsA in one cohort study [≥3 sites: HR 2.24 (95% CI 1.23-4.08)], one case-control study [body surface area >75%: OR 2.52 (95% CI 1.33-4.75)] and three cross-sectional studies. The meta-analysis suggested a trend for an association between high PASI and PsA risk [mean difference 3.39 (95% CI 0.94-5.83)]. Therefore, psoriasis patients with such clinical features may require a particular attention for early and close detection of PsA during the course of the cutaneous disease.

Symptoms dermatologists should look for in daily practice to improve detection of psoriatic arthritis in psoriasis patients: an expert group consensus.

BACKGROUND: Up to 29% of patients with psoriasis seen by dermatologists have undiagnosed psoriatic arthritis (PsA). As early detection of PsA may be associated with improved joint and skin outcomes, it is essential for dermatologists to improve their ability to diagnose PsA. Skin and nail features of psoriasis associated with PsA are well known to dermatologists but they may feel less confortable assessing other symptoms and they rarely use PsA screening questionnaires. OBJECTIVE: To develop a limited list of clinical signs and symptoms that a dermatologist should be looking for in a psoriasis patient in addition to specific skin features and nail involvement, to improve PsA detection. METHODS: A systematic search was performed in Pubmed, Cochrane and Embase databases to identify clinical key symptoms associated with PsA. It yielded 27 studies in which we extracted a list of clinical signs and symptoms observed in PsA and submitted it to a panel of dermatology experts through a DELPHI selection process. The experts had to determine which minimal set of signs and symptoms dermatologists should look for in daily practice to improve detection of PsA in patients with psoriasis. RESULTS: The four items that received a score higher than 90% in the DELPHI process were finally selected. Those items were as follows: peripheral inflammatory pain (100%), axial inflammatory pain (95.3%), dactylitis (93%), buttock and sciatic pain (90.7%). The remaining items: distal interphalangeal joints (DIPs) involvement (83.7%), Talalgia (79.1%), swollen Achille's tendon (41.9%), costo-chondral involvement (32.6%), uveitis (7%), mouth ulcerations (2.3%), were not retained. CONCLUSION: We propose a set of four items to screen psoriasis patients for psoriatic arthritis for routine clinical use by dermatologists.

Treatment (biotherapy excluded) of psoriatic arthritis: an appraisal of methodological quality of international guidelines.

BACKGROUND: Some international guidelines have been published to provide the best care for patients with psoriatic arthritis (PsA) but little is known about their quality. OBJECTIVE: The primary aim of this study was to examine the quality of guidelines that concern treatment (biotherapy exluded) of PsA. The secondary aim was to review studies published since the publication of the most recent guideline. METHODS: A systematic literature search was carried out from 2007 to February 2013, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including 'Arthritis, Psoriatic/therapy' NOT 'Biological Therapy' OR 'Antibodies, Monoclonal' OR 'Recombinant Fusion Proteins' OR 'tumour necrosis factor-alpha'. The AGREE instrument (Appraisal of Guidelines Research and Evaluation) was used by four reviewers to evaluate the quality of selected guidelines according to the proposed methodology. RESULTS: Of the 518 identified references, six guidelines and two studies were selected. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well-addressed domains were 'applicability', 'stakeholder involvement', 'scope and purpose' and 'quality of development', whereas 'editorial independence' and 'clarity and presentation' were less problematic. CONCLUSION: Although guidelines development was of good quality, many of the studies that they included are of poorer quality. This work indicates that the current guidelines can be improved, particularly the stakeholder domain and the applicability domain. The prospective use of the AGREE instrument should improve the guideline quality. More controlled trials should be required but are unlikely to be conducted, given the lack of interest in studying old drugs.

Open low-field magnetic resonance imaging for target definition, dose calculations and set-up verification during three-dimensional CRT for glioblastoma multiforme.

AIMS: To assess the effect on target delineation of using magnetic resonance simulation for planning of glioblastoma multiforme (GBM). Dose calculations derived from computed tomography- and magnetic resonance-derived plans were computed. The accuracy of set-up verification using magnetic resonance imaging (MRI)-based digital reconstructed radiographs (DRRs) was assessed. MATERIALS AND METHODS: Ten patients with GBM were simulated using computed tomography and MRI. MRI was acquired with a low-field (0.23 T) MRI unit (SimMRI). Gross tumour volumes (GTVs) were delineated by two radiation oncologists on computed tomography and MRI. In total, 30 plans were generated using both the computed tomography, with (planbathoCT) and without (planCT) heterogeneity correction, and MRI data sets (planSimMRI). The minimum dose delivered (Dmin) to the GTV between computed tomography- and MRI-based plans was compared. The accuracy of set-up positioning using MRI DRRs was assessed by four radiation oncologists. RESULTS: The mean GTVs delineated on computed tomography were significantly (P<0.001) larger than those contoured on MRI. The mean (+/-standard deviation) Dmin difference percentage was 0.3+/-0.8, 0.1+/-0.6 and -0.2+/-1.0% for the planCT/planbathoCT-, planCT/planSimMRI- and planbathoCT/planSimMRI-derived plans, respectively. The set-up differences observed with the computed tomography and MRI DRRs ranged from 1.0 to 4.0 mm (mean 1.5 mm; standard deviation+/-1.4). CONCLUSIONS: GTVs defined on computed tomography were significantly larger than those delineated on MRI. Compared with computed tomography-derived plans, MRI-based dose calculations were accurate. The precision of set-up verifications based on computed tomography- and MRI-derived DRRs seemed similar. The use of MRI only for the planning of GBM should be further assessed.

Open magnetic resonance imaging using titanium-zirconium needles: improved accuracy for interstitial brachytherapy implants?

PURPOSE: To evaluate the benefit of using an open magnetic resonance (MR) machine and new MR-compatible needles to improve the accuracy of brachytherapy implants in pelvic tumors. METHODS AND MATERIALS: The open MR machine, foreseen for interventional procedures, allows direct visualization of the pelvic structures that are to be implanted. For that purpose, we have developed MR- and CT-compatible titanium-zirconium (Ti-Zr) brachytherapy needles that allow implantations to be carried out under the magnetic field. In order to test the technical feasibility of this new approach, stainless steel (SS) and Ti-Zr needles were first compared in a tissue-equivalent phantom. In a second step, two patients implanted with Ti-Zr needles in the brachytherapy operating room were scanned in the open MR machine. In a third phase, four patients were implanted directly under open MR control. RESULTS: The artifacts induced by both materials were significantly different, strongly favoring the Ti-Zr needles. The implantation in both first patients confirmed the excellent quality of the pictures obtained with the needles in vivo and showed suboptimal implant geometry in both patients. In the next 4 patients, the tumor could be punctured with excellent accuracy, and the adjacent structures could be easily avoided. CONCLUSION: We conclude that open MR using MR-compatible needles is a very promising tool in brachytherapy, especially for pelvic tumors.

Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume.

PURPOSE: One of the components of radiotherapy (RT) in medulloblastoma/primitive neuroectodermal tumors is the prophylactic irradiation of the whole brain (WBI). With the aim of reducing late neuropsychologic morbidity a CT-scan-based dosimetric study was undertaken in which treatment was confined mainly or exclusively to supratentorial sites considered at high risk for disease recurrence. METHODS AND MATERIALS: A comparative dosimetric study is presented in which a three field (two laterals and one posterior) proton plan (spot scanning method) is compared with a two-field conventional WBI 6 MV x-ray plan, to a 6-field "hand-made" 6 MV x-ray plan, and to a computer-optimized 9-field "inverse" 15 MV x-ray plan. For favorable patients, 30 Gy were delivered to the ventricles and main cisterns, the subfrontal and subtemporal regions, and the posterior fossa. For the unfavorable patients, 10 Gy WBI preceeded a boost to 30 Gy to the same treatment volume chosen for favorable patients. The dose distribution was evaluated with dose-volume histograms to examine the coverage of the targets as well as the dose to the nontarget brain and optical structures. In addition, the risks of radiation-related late neuropsychologic effects after WBI were collected from the literature and used to predict normal tissue complication probabilities (NTCPs) for an intelligence quotient deficit after treatment with photon or proton beams. RESULTS: Proton beams succeeded better in reducing the dose to the brain hemispheres and eye than any of the photon plans. A 25.1% risk of an IQ score <90 was predicted after 30 Gy WBI. Almost a 10% drop in the predicted risk was observed when using proton beams in both favorable and unfavorable patients. However, predicted NTCPs for both optimized photon plans ("hand made" and "inverse") were only slightly higher (0.3-2.5%) than those of proton beams. An age-modifying factor was introduced in the predictive NTCP model to assess for IQ differences in relation with age at irradiation. Children with ages between age 4 to 8 benefitted most from the dose reduction in this exercise (similar NTCP predictions for both proton and "inverse" plans). CONCLUSION: Modulated proton beams may help to significantly reduce the irradiation of normal brain while optimally treating the supratentorial subsites at higher risk for relapse. A decrease in morbidity can be expected from protons and both optimized proton plans compared to WBI.

Influence of modifications in breast irradiation technique on dose outside the treatment volume.

PURPOSE: There is increasing interest in potential long-term effects of radiotherapy (RT) in patients treated for breast cancer, particularly those in whom long-term survival can be expected. The purpose of the present study was to determine the effects of treatment techniques, including patient positioning (supine vs. prone) on the absorbed dose in organs at a distance from the treatment volume in breast RT. METHODS AND MATERIALS: Dose distribution was studied in a Rando-Alderson phantom, modified with a simulated left breast of tissue-equivalent material. RT delivery was studied using 60Co and 6 MV x-ray beams, as well as electrons and a 192Ir source for tumor bed boost RT. Doses were measured in several organs and tissues of interest using LiF thermoluminescent dosimeters. Tangential breast RT was simulated using both supine and prone positioning. RESULTS: Peripheral doses generally decreased approximately exponentially with distance from the edge of the treatment field. Peripheral doses in various target organs were significantly higher for supine than for prone tangential breast RT (for 50 Gy prescribed dose): 0.50 Gy vs. 0.25 Gy for the upper abdomen, 0.05 Gy vs. 0.02 Gy for pelvic organs, 0.17 Gy vs. 0.08 Gy for active bone marrow, and 0.47 Gy vs. 0.12 Gy for ipsilateral lung (discounting lung in primary beam). CONCLUSIONS: The present study suggests that peripheral doses in several organs and tissues of interest can be reduced by 40 to 75% by prone tangential breast RT. These results may have implications for future strategies in the treatment of screen-detected breast cancer.

Patient positioning in prostate radiotherapy: is prone better than supine?

PURPOSE: To assess potential dose reductions to the rectum and to the bladder with three-dimensional conformal radiotherapy (3D-CRT) to the prostate in the prone as compared with the supine position; and to retrospectively evaluate treatment position reproducibility without immobilization devices. METHODS AND MATERIALS: Eighteen patients with localized prostate cancer underwent pelvic CT scans and 3D treatment planning in prone and supine positions. Dose-volume histograms (DVHs) were constructed for the clinical target volume, the rectum and the bladder for every patient in both treatment positions. "Comparative DVHs" (cDVHs) were defined for the rectum and for the bladder: cDVH was obtained by subtracting the organ volume receiving a given dose increment in the prone position from the corresponding value in the supine position. These values were then integrated over the entire dose range. The prescribed dose to the planning target volume (PTV) was 74 Gy using a 6-field technique. To evaluate reproducibility, portal films were subsequently reviewed in 12 patients treated prone and 10 contemporary patients treated supine (controls). No immobilization devices were used. Deviations in the anterio-posterior (X) and cranio-caudal (Y) axes were measured. Mean treatment position variation, total setup variation, systematic setup variation, and random setup variation were obtained. RESULTS: Prone position was associated with a higher dose to the rectum or to the bladder in 6 (33%) and 7 (39%) patients, respectively. A simultaneously higher dose to rectum and bladder was noted in 2 (11%) patients in prone and in 7 (39%) patients in supine. Rectal and bladder volumes were frequently larger in prone than in supine: mean prone/supine volume ratios were 1.21 (SD, 0.68) and 1.03 (SD, 1.32), respectively. In these cases cDVH analysis more often favored the prone position. Mean treatment position variation and total setup variation were similar for both prone and supine plans. A higher systematic setup variation was observed in prone positioning: 2.7 mm vs. 1.9 mm (X axis) and 4.1 mm vs. 2.2 mm (Y axis). The random variation was similar for both prone and supine: 4. 0 mm vs. 3.6 mm (X axis) and 3.7 mm vs. 3.6 mm (Y axis). CONCLUSIONS: Prone position 3D-CRT is frequently, but not always, associated with an apparent dose reduction to the rectum and/or to the bladder for prostate cancer patients. As suggested by the increased mean prone/supine rectal volume ratio, the advantage of prone positioning for the rectum may be artifactual, at least partly reflecting a position-dependent rectal air volume, which may significantly vary from treatment to treatment. In the absence of immobilization devices, daily setup reproducibility appears less accurate for the prone position, primarily due to systematic setup variations.

Feasibility and tolerance of pulsed dose rate interstitial brachytherapy.

PURPOSE: Pulsed dose rate (PDR) treatment is a new approach that associates the physical advantages of high-dose-rate (HDR) technology with the potential radiobiological advantages of low-dose-rate (LDR) brachytherapy. This retrospective study analyzes the feasibility, toxicity, and preliminary oncologic results in a series of 43 patients treated with PDR interstitial brachytherapy. METHODS AND MATERIALS: Twenty-four patients with pelvic, 17 patients with head and neck, and 2 patients with breast cancers were treated. Twenty-eight patients had primary and 15 recurrent tumors; 14 had received prior external irradiation to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy (median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium source (PDR Nucletron Micro-Selectron). RESULTS: The median treated volumes (at the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40 cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer procedures, 3 technical machine failure events were observed (0.02%). Grade 3 acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula). Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis. With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6 pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3 pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are lost to follow-up. CONCLUSION: PDR interstitial brachytherapy for pelvic, head and neck, and breast malignancies is feasible and the acute and late toxicities seem acceptable. Although the physical advantages of PDR are clear, further follow-up is required to determine how results compare with those obtained with standard LDR brachytherapy.

Radiotherapy of bladder cancer: relevance of bladder volume changes in planning boost treatment.

PURPOSE: This study aims to evaluate tumor motion with controlled changes of the bladder volume, and to assess the reproducibility of bladder (and tumor) position using a urinary catheter balloon as an immobilization device. METHODS AND MATERIALS: First, three patients with tumor growths in three different bladder regions (trigone, left lateral wall, anterior wall) were evaluated. Three-dimensional CT-based reconstructed images were used to measure the displacement of the tumors when 100 cc were removed from a bladder originally filled with 170 cc of contrast. The 3D calculated boost beam arrangements and field sizes for the three tumors in the partially emptied bladders were used to simulate treatment of the same tumors in the maximally filled bladders. Dose-volume histograms were obtained. Second, verification of an ellipsoid model for bladder volume changes was undertaken in 41 patients. Third, in eight additional patients a urinary catheter balloon filled with 80-cc sterile saline solution was used in an attempt to reproduce the shape and spatial coordinates of the bladder during the boost treatment. A pair of orthogonal films with the 80-cc balloon filled with contrast material were taken at simulation and repeated twice at weekly intervals during radiotherapy. The reproducibility was quantified by sequentially calculating the common surface of the bladder images in each orthogonal view. RESULTS: Target motion, especially in the craniocaudal axis, appeared to be more relevant for tumors arising in the bladder walls (15 mm) than in the trigone (5 mm). Underdosage (<95% of the prescribed dose to the target volume) was observed in 20, 20, and 50% (with 1 cm margins around the tumor) and in 10, 10, and 15% (with 1.5 cm margins around the tumor) of the tumors arising in the trigone, left lateral wall, and anterior wall, respectively. The ellipsoidal model was validated with a strong correlation coefficient allowing to establish a predictive model for bladder wall displacements as a function of bladder volume. In the balloon reproducibility study, mean reproducibility factors of 0.84 (+/-0.06) and 0.82 (+/-0.07) were obtained for both anteroposterior and lateral views, respectively. CONCLUSIONS: Changes in bladder volume and shape related to bladder filling can result in clinically significant displacements of the target volume. A minimum of 2-cm margins around the target may compensate for extreme bladder volume changes during boost treatment. An ellipsoidal model for the bladder is consistent with these observations. Although an 80-cc urinary catheter balloon helped to immobilize the bladder, reproducibility was less than perfect.

Dose variation at bone/titanium interfaces using titanium hollow screw osseointegrating reconstruction plates.

PURPOSE: To evaluate dose variations at bone/titanium interfaces in an experimental model designed to simulate postoperative radiotherapy in patients with mandibular reconstructions using a titanium hollow-screw osseointegrating reconstruction plate (THORP) system. MATERIALS AND METHODS: The model consisted of a 25 x 25 x 10 mm3 block of fresh bovine femoral diaphysis, to the surface of which a segment of THORP system reconstruction plate was fixed by means of a solid titanium screw 4 mm in diameter and 10 mm in length. Using specially designed thermoluminescent dosimeters (TLD) 2 mm in diameter and 0.13 mm in thickness, dose measurements were carried out at four distances from the screw axis (0.1, 0.3, 0.6, and 1 mm). 60Co and 6-MV photon beams were used at incidences both perpendicular and parallel ("axial") to the screw axis. RESULTS: For 6-MV X-ray beams incident perpendicular to the screw axis, the maximum dose enhancement (due to backscatter) and the maximum dose reduction (due to attenuation) at the bone/titanium interface were 5% (+/- 2%) and 6% (+/- 2%), respectively. The corresponding values for 60Co beams were 6% (+/- 5%) and 10% (+/- 5%). For the axial incidences, a maximum dose enhancement of 5-7% was noted for both 6-MV X-rays and 60Co for beams incident on the surface containing the THORP plate segment, whereas beams incident on the opposite surface induced only a very small dose enhancement (2-3%). CONCLUSION: Using a new experimental model, TLD measurements showed only marginally significant dose variations at bone/titanium interfaces around THORP screws, all measured values being very close to the uncertainty limits (+/- 5%) associated with the method. For both 60Co and 6-MV beams, dose variations appeared smaller for axial than for perpendicular incidences. Because photon beams used in head and neck cancer treatment are most often directed parallel to the screw axes, these results suggest that failures of prosthetic osseointegration are unlikely to be explained by an overdosage at the bone/titanium interface.

Can a total body irradiation technique be fast and reproducible?

PURPOSE: Total body irradiation (TBI) is frequently a complex and time-consuming technique that significantly overloads Radiation Oncology departments. In an attempt to shorten TBI setup and treatment time we aimed to develop a system where the lung blocks are fixed with optimal precision to the build-up booster lucite screen while the patient is immobilized in a reproducible upright position. METHODS AND MATERIALS: Fifteen patients diagnosed with leukemia were conditioned before bone marrow transplant since March 1992. Patients were immobilized in a semistanding position in a special stand with arm bars and hand grips. Treatment was delivered with a 6 MV x-ray horizontal beam. Six fractions of 2.25 Gy (mean instantaneous dose rate of 13.8 +/- 3.8 cGy/min) were delivered twice a day over 3 days (total dose: 13.5 Gy). Each fraction was given in alternating AP (facing the beam) and PA (turning the back) projections. Customized lung blocks (35% transmission) were used to assure a maximum lung dose of 10 +/- 0.5 Gy. The blocks were taped to a 1 cm thick lucite screen interposed between the source and the patient. Lung shields were checked by port films before each fraction. The reproducibility of the patient's positioning (and lung shielding) was evaluated by measuring the horizontal and vertical deviations of the infero-external corners of the lung blocks in the port films in relation to the same point in the simulation films. In vivo dosimetry (thermoluminescence and diodes) was performed by placing dosimeters and probes in the central axis and in several off-axis sites. RESULTS: The mean horizontal and vertical deviations were 3.5 +/- 4.1 mm and 7.5 +/- 5.9 mm for the anterior fields, and 4.1 +/- 4.1 mm and 6.9 +/- 6.4 mm for the posterior fields. An acceptable position of the blocks was considered when deviations were < 5 mm horizontally and/or < 10 mm vertically. The mean time per fraction (i.e., interval between the patient's entering and leaving the treatment room) was 35 +/- 5 min. CONCLUSIONS: A satisfactory level of reproducibility can be reached with this technique. The reasonably short treatment time contributes to reproducibility and patient comfort.

Intra-arterial 90Y brachytherapy: preliminary dosimetric study using a specially modified angioplasty balloon.

PURPOSE: Irradiation has been shown to be effective in preventing restenosis after dilatation in human peripheral arteries. We have developed a dedicated system for coronary intraarterial irradiation using a 90Y pure beta-emitting source inside a specially modified angioplasty balloon. This paper presents a preliminary dosimetric evaluation of this system. METHODS AND MATERIALS: Specially fabricated titanium-covered and activated yttrium wires (outer diameter 0.32 mm) were used for these studies. Dosimetry was performed using small thermoluminescent dosimeters (TLDs) placed on the surface of the 2-cm long angioplasty balloons, inflated with contrast medium to a diameter of 2.5, 3, 3.5, and 4 mm. Radioactive 90Y wires were left in the inner balloon catheter and the surface dose rate was measured and extrapolated to 72 h after activation to allow a comparison between the values obtained. After observing the poor centering of the source within the standard angioplasty balloon, a new centering balloon was developed. A conventional balloon was subdivided into four evenly spaced interconnecting chambers, thus assuring adequate centering of the inner catheter. Thermoluminescent dosimetric measurements were performed with a 3.5 mm centering balloon to evaluate the homogeneity of the surface doses compared to those measured with the conventional balloon. RESULTS: Thermoluminescent dosimetric measurements using the standard balloons filled with contrast medium were plotted semilogarithmically as a function of distance from the balloon surface. The logarithms of the measured doses fit a straight line as a function of depth. The doses at 1 mm and 3 mm are approximately 50 and 10% of the surface dose, respectively. Due to the poor centering of the source in the conventional balloons, the dispersion and standard deviations (SDs) of the measured surface doses increased proportionally to the balloon diameter (SDs are 1.89, 5.52, 5.79, and 6.46 Gy for 2.5, 3, 3.5, and 4 mm balloon diameters, respectively). For the 3.5 mm centering and conventional balloons the respective mean, minimum, and maximum surface doses were 8.41 Gy (min. 7.26; max. 9.46) and 7.89 Gy (min. 2.18; max. 16.06) and their standard deviations were 0.66 and 5.79 Gy, respectively. CONCLUSIONS: Conventional angioplasty balloons cannot ensure a homogeneous dose delivery to an arterial wall with an intralumenal 90Y beta source. Preliminary dosimetric results using a modified centering balloon show that it permits improved surface dose distribution (axial and circumferential homogeneity), making it suitable for clinical applications.

High dose rate brachytherapy for prevention of restenosis after percutaneous transluminal coronary angioplasty: preliminary dosimetric tests of a new source presentation.

PURPOSE: Balloon dilatation of coronary artery stenosis has become a standard treatment of atherosclerotic heart disease. Restenosis due to excessive intimal cell proliferation, which subsequently occurs in 20-50% of patients, represents one of the major clinical problems in contemporary cardiology, and no satisfactory method for its prevention has thus far been found. Because modest doses of radiation have proved effective in preventing certain types of abnormal cellular proliferation resulting from surgical trauma, and brachytherapy has already been used successfully after dilation of peripheral arteries, development of a radioactive source suitable for coronary artery applications would be of great interest. METHODS AND MATERIALS: Nonradioactive flexible yttrium-89 wires (diameter of 0.15 and 0.26 mm) were activated within the thermal neutron flux of an experimental reactor. Standard angioplasty balloons (2 cm long, 2.5 mm in diameter when inflated) were inserted for dosimetry into a specially manufactured tissue equivalent phantom. Four wells, drilled perpendicular to the axis of the balloon, allowed for the insertion of thermal luminescent dosimeters (TLDs; 2 mm of diameter) and spacers. The angioplasty balloon was inflated with air or with contrast media. Radioactive yttrium-90 wires were left in the central lumen of the balloon for 2 min. Doses at the surface of the balloon, and at 1, 2, and 3 mm were determined from TLD readings. RESULTS: Doses obtained at the surface of the balloon, for a 2-min exposure for the 0.26 mm wire (balloon inflated with air) and the 0.15 mm wire (air or contrast), were 56.5 Gy, 17.8 Gy, 5.4 Gy, respectively. As expected for a beta emitter, the fall-off in dose as a function of depth was rapid. External irradiation from the beta source was negligible. CONCLUSIONS: Our experiments indicate that the dose rates attainable at the surface of the angioplasty balloon using this technique allow the doses necessary for the inhibition of intimal cell proliferation to be reached within a relatively short period of time. The thin yttrium-90 wires are very easy to handle, and their mechanical and radioactive properties are well suited to the requirements of the catheterization procedure.

A novel system for intracoronary beta-irradiation: description and dosimetric results.

PURPOSE: A dosimetric evaluation of a new device dedicated to intravascular irradiation, associating a beta source and a centering device, was carried out before initiation of a clinical pilot study. METHODS AND MATERIALS: A 29-mm-long 90Y coil, coated with titanium and fixed to the end of a thrust wire, was introduced into the inner lumen of purpose-built centering balloons of different diameters (2.5, 3, 3.5, and 4 mm). Dose homogeneity was evaluated by studying both axial and circumferential dose variations, based on readings from thermoluminescent dosimeters (TLDs) placed on the balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral balloon segments with those located on segments adjacent to the midpoint of the source. The centering ability of the device was studied by comparing measurements on opposing surfaces of the balloon. The dose attenuation by water and contrast medium was evaluated and compared with that in air. The balloon contamination was studied using a contamination counter. The total 90Y coil activity was measured by liquid scintillation to relate activity to surface dose. RESULTS: Activity-surface dose correlation showed that for a linear coil activity of 1 mCi/mm, the mean dose rate at the surface of a 2.5-mm balloon filled with contrast medium was 8.29 Gy/min. The doses at the surface of larger balloons (3, 3.5, and 4 mm) filled with contrast were 78%, 59%, and 47%, respectively, of the dose measured at the surface of the 2.5-mm balloon. The coefficient of variation (CV) in surface dose for 2.5-, 3-, 3.5-, and 4-mm centering devices filled with contrast medium were 9%, 8%, 9%, and 12%, respectively. There was no statistically significant difference between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a 2.5-mm balloon, compared with air the dose attenuation by water and contrast medium was similar (0.70 and 0.69, respectively), but a significant difference was seen between the readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p < 0.001). No contamination was found in the balloon shaft after source retrieval. CONCLUSION: The dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within the centering balloons. The achievable dose rates will permit intravascular irradiation within a short time interval. The absence of residual balloon contamination after source retrieval meets the requirements for a sealed source used in a clinical setting.

Seminoma of the testis: is scrotal shielding necessary when radiotherapy is limited to the para-aortic nodes?

PURPOSE: To evaluate the influence of different shielding conditions and field geometry on the scatter dose to the remaining testicle during postoperative radiotherapy (RT) in seminoma. MATERIALS AND METHODS: Testicular dose measurements were made with LiF thermoluminescent dosimeters (TLD) in 29 patients with stage I and IIA seminoma. The target volume consisted of para-aortic (PA) and para-aortic and homolateral iliac (PAI) lymph nodes in 14 and 15 patients, respectively. All patients had a scrotal shield as well as an additional block extending 7 cm inferiorly from the caudal field edge to shield the testicle from external scatter and collimator leakage. Doses with and without testicular blocks were measured for all patients. In seven patients treated exclusively to the PA region the gonadal dose was assessed according to four different shielding conditions: without any protection, with a gonadal shield alone, with the addition of an inferior field border block to the gonadal shield, and with the field border block alone. RESULTS: For patients treated with PAI fields the mean testicular doses per fraction were 3.89 cGy (S.D. +/- 1.44) and 1.48 cGy (S.D. +/- 0.51) without and with gonadal shielding, respectively (P-value < 0.001); the corresponding values for PA fields were 1.86 cGy (S.D. +/- 0.86) and 0.65 cGy (S.D. +/- 0.35). For the patients treated to the PA region and assessed according to the four different shielding conditions, the additional external block to the testicular shield did not reduce significantly the measured dose on the testis. CONCLUSIONS: These results suggest a benefit of gonadal shielding even in seminoma patients undergoing radiotherapy limited to the para-aortic region.

Bladder opacification does not significantly influence dose distribution in conformal radiotherapy of prostate cancer.

PURPOSE: To compare the results of treatment planning with or without bladder contrast during simulation of three dimensional conformal radiotherapy (3D-CRT) for prostate cancer (18 MV X-rays, six field arrangement), and to assess the potential changes in dose distribution in the target and rectal volumes. METHODS AND MATERIALS: Based on CT-simulation using intravenous contrast media, 3-D conformal treatment planning was performed in five patients. To simulate a non-opacified bladder, the electron matrix density of the opacified bladder was virtually changed to water density. Two treatment plans were carried out, with and without bladder opacification. In each patient dose distributions were formally compared for both plans, and the increment in monitor units (MU) needed to compensate for the presence of contrast media was assessed. RESULTS: A mean dose variation of -0.03% (range, -0.03-0.14%) and -1.13% (range, -1.85-0%) was observed for the prostate and the rectum, respectively. The average mean MU increment without bladder contrast normalized to the case with bladder contrast was 0.31% +/- 0.52. CONCLUSIONS: Bladder opacification used during simulation does not significantly influence prostate or rectal dose distributions in prostate patients treated with 3D-CRT, 18 MV X-rays, and a six-beam arrangement.

Reproducibility of conformal radiation therapy in localized carcinoma of the prostate without rigid immobilization.

The reproducibility of 3-dimensional (3D) conformal therapy in localized prostate cancer was studied in 14 patients, based on retrospective analysis of 196 anteroposterior-posteroanterior (AP/PA) and lateral portal images. The patients were treated supine without rigid immobilization using six isocentric coplanar conformal fields. Three different observers independently compared the portal and simulation images, determining the deviation of each portal film from the corresponding simulation film. No significant deviations were observed in the cephalo-caudal or lateral axes (0 mm median values). However, a systematic median shift of 5 mm (0 to + 10, range) was observed in the anteroposterior direction, presumably as a consequence of a sagging in the treatment couch under the patient's weight. After modification of the treatment couch, no further systematic anteroposterior shifts have been observed. These results demonstrate that the daily setup of conformal prostate irradiation fields can be performed with acceptable reproducibility without the use of special immobilization devices.