Multi-centre real-world validation of automated treatment planning for breast radiotherapy.

PURPOSE: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices. METHODS: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units. RESULTS: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart Dmean, 16.7 % for ipsilateral lung Dmean, and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D0.03cc, D5% and Dmean, respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability. CONCLUSION: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans.

Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma.

OBJECTIVE: To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). METHODS AND MATERIALS: From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ''In-Field (IF)'', "Marginal recurrence" or ''Out-of-Field (OF)'' if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. RESULTS: We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6-28.9 cc), while the mean MTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61-91%) and 4 recurrences were marginal to MTVpre (1-33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). CONCLUSION: Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.

Free-to-use DIR solutions in radiotherapy: Benchmark against commercial platforms through a contour-propagation study.

PURPOSE: A contour propagation study has been conducted to benchmark three algorithms for Deformable Image Registration (DIR) freely available online against well-established commercial solutions. METHODS: ElastiX, BRAINS and Plastimach, available as modules in the open source platform 3DSlicer, were tested as the recent AAPM Task group 132 guidelines proposes. The overlap of the DIR-mapped ROIs in four computational anthropomorphic phantoms was measured. To avoid bias every algorithm was left to run without any human interaction nor particular registration strategy. The accuracy of the algorithms was measured using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. The registration quality was compared to the recommended geometrical accuracy suggested by AAPM TG132 and to the results of a large population-based study performed with commercial DIR solutions. RESULTS: The considered free-to-use DIR solutions generally meet acceptable accuracy and good overlap (DSC > 0.85). Mild failures (DSC < 0.75) were detected only for the smallest structures. In case of extremely severe deformations acceptable accuracy was not met (MDC > 3 mm). The morphing capability of the tested algorithms equals those of commercial systems when the user interaction is avoided. Underperformances were detected only in cases where a specific registration strategy is mandatory to obtain a satisfying match. CONCLUSIONS: All of the considered algorithms show performances not inferior to previously published data and have the potential to be good candidates for use in the clinical routine. The results and conclusions only apply to the considered phantoms and should not be considered to be generally applicable and extendable to patient cases.

Pseudoangiomatous stromal hyperplasia (PASH) presenting as axillary lump: case report and review of the literature.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign mesenchymal breast lesion. There are extremely rare reports of PASH arising in accessory breast tissue. To date, in literature, fewer than 10 cases of PASH occurring in axillary region have been described. We report a case presenting as axillary lump in a young woman. A 20-year-old female presented to our surgical unit for a progressively growing and painful palpable mass of the right axilla for about a year. Before surgery an ultrasound was performed. The patient underwent local excision of the lesion under local anaesthesia. Through histological and immunohistochemical examination a pseudoangiomatous stromal hyperplasia (PASH) was diagnosed. At 6 months of followup the patient is free of disease. It is important to include PASH also in the differential diagnosis of axillary lumps. Histological examination of the surgical specimen and surgery represent, respectively, the mainstay for diagnosis and therapy.

Usefulness of capillary electrophoresis-based multiplex PCR assay for species-specific identification of Candida spp.

The study evaluated the performances of a commercial multiplex PCR assay, the Seegene Seeplex STI Master Panel 3, for Candida spp. identification. Eighty clinical strains of Candida spp. were identified with this system and a homemade multiplex PCR assay. The results were also compared with those obtained with two phenotypic methods. The study provided a preliminary evaluation of a multiplex assay from Seegene that uses capillary electrophoresis as the detection of amplified products. The Seeplex assay was found to be a rapid and useful method for identifying large numbers of yeast isolates in the clinical laboratory context.

An XPS analytical approach for elucidating the microbially mediated enargite oxidative dissolution.

In this work, the microbe-mediated oxidative dissolution of enargite surfaces (Cu(3)AsS(4)) was studied on powdered samples exposed to 9K nutrient solution (pH 2.3) inoculated by Acidithiobacillus ferrooxidans initially adapted to arsenopyrite. These conditions simulate the acid mine environment. The redox potential of the inoculated solutions increased up to +0.72 V vs normal hydrogen electrode (NHE), indicating the increase of the Fe(3+) to Fe(2+) ratio, and correspondingly the pH decreased to values as low as 1.9. In the sterile 9K control, the redox potential and pH remained constant at +0.52 V NHE and 2.34, respectively. Solution analyses showed that in inoculated medium Cu and As dissolved stoichiometrically with a dissolution rate of about three to five times higher compared to the sterile control. For the first time, X-ray photoelectron spectroscopy (XPS) was carried out on the bioleached enargite powder with the aim of clarifying the role of the microorganisms in the dissolution process. XPS results provide evidence of the formation of a thin oxidized layer on the mineral surface. Nitrogen was also detected on the bioleached surfaces and was attributed to the presence of an extracellular polymer substance layer supporting a mechanism of bacteria attachment via the formation of a biofilm a few nanometers thick, commonly known as nanobiofilm.

Threshold segmentation for PET target volume delineation in radiation treatment planning: the role of target-to-background ratio and target size.

A multivariable approach was adopted to study the dependence of the percentage threshold [TH(%)] used to define the boundaries of 18F-FDG positive tissue on emission scan duration (ESD) and activity at the start of acquisition (Aacq) for different target sizes and target-to-background (T/B) ratios. An anthropomorphic model, at least for counting rate characteristics, was used to study this dependence in conditions resembling the ones that can be encountered in the clinical studies. An annular ring of water bags of 3 cm thickness was fitted over an International Electro-technical Commission (IEC) phantom in order to obtain counting rates similar to those found in average patients. The scatter fraction of the modified IEC phantom was similar to the mean scatter fraction measured on patients, with a similar scanner. A supplemental set of microhollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner field of view. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL. The ESD was set to 60, 120, 180, and 240 s/bed. Data were fitted using two distinct multiple linear regression models for sphere ID < or = 10 mm and sphere ID > 10 mm. The fittings of both models were good with an R2 of 0.86 in both cases. Neither ESD nor Aacq resulted as significant predictors of the TH(%). For sphere ID < or =10 mm the target size was the most significant predictor of the TH(%), followed by the T/B ratio, while for sphere ID > 10 mm the explanatory power of the target size and T/B ratio were reversed, the T/B ratio being now the most important predictor of the TH(%). Both the target size and T/B ratio play a major role in explaining the variance of the TH(%), throughout the whole range of target sizes and T/B ratios examined. Thus, algorithms aimed at automatic threshold segmentation should incorporate both variables with a relative weight which critically depends on target size.

HCV infection and chronic arthritis: Does viral replication matter?

BACKGROUND: HCV infection beside chronic hepatitis can induce immunological disorders with different clinical expressions such as chronic arthritis. AIM: To study the prevalence of arthritis in HCV-Ab positive patients and verify possible correlation with viral replication, hepatic damage and autoimmunity imbalance. STUDY DESIGN: Three hundred and eighty patients (196 M and 184 F) affected by HCV infection were examined and 38 (10%) were selected according to the presence of arthritis. Eight of them were excluded because arthritis raised before HCV infection. Each patient, once undergone liver biopsy, was evaluated for: clinical examination (articular evolution), Rx examination, serum expression of hepatic damage (mainly ALT), viral replication, and involvement of autoimmunity (ANA, RF, crioglobulins, AKA, CCP). RESULTS: Data from patients [Lamprecht P, Gause A, Gross WL. Cryoglobulinemic vasculitis. Arthritis Rheum 1999; 42:2507-16.] with AKA and CCP positivity were not considered for statistical examination because the clear correlation between rheumatoid arthritis and these parameters. The remaining 20 patients showed hepatic damage 47%, viral replication in 74%, RF 42%, ANA 16%, crioglobulins 42% (RF positive). No correlation was evident between ANA serum concentrations and viral replication; furthermore a significant negative correlation between RF positivity and viral replication only in a subgroup of patients with serologic expression of hepatic damage was found. CONCLUSIONS: These data support hypothesis that the onset of arthritis and presence of autoimmunity parameters ANA, RF are not related to the viral replication but others mechanism immunological induced by HCV might be considered.

Neutron production from a mobile linear accelerator operating in electron mode for intraoperative radiation therapy.

Intraoperative electron beam radiotherapy is increasingly performed using mobile linac delivering therapeutic radiation doses in unshielded operating rooms. While no special neutron-shielding problem should arise for operation at 10 MeV or less, it is not clear whether this holds true for operation at higher energies. This paper reports the measured neutron production from a Mobetron mobile electron linac, operated at 12 MeV, and compares the results with those from a conventional linac, also operated at 12 MeV in electron mode. Neutron leakage measurements were performed by means of passive bubble detectors in the scattering foil, patient and floor planes. Neutron dose equivalent rates per unit of electron dose delivered by the Mobetron at its normal treatment distance (50 cm SSD) were 0.33 microSv Gy(-1) at the accelerator head, 0.18 microSv Gy(-1) in the patient plane at 15 cm from the beam axis and 0.31 microSv Gy(-1) at the floor plane, on the beam axis and under the beam stopper. For a weekly workload of 250 Gy, the weekly neutron dose equivalents at 12 MeV for the Mobetron at a distance of 300 cm from the scattering foil were 14.3 and 1.7 microSv/week for floor below and adjoining areas on the same floor, respectively. Neutron dose equivalent rates generated from Mobetron are at least one order of magnitude lower than ones produced by a conventional linac operated at the same energy in electron mode. Mobetron can be used at 12 MeV in an unshielded operating room for a weekly workload of up to 250 Gy if the bremsstrahlung x-rays are shielded to negligible levels.

Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: 99mTc-ECD brain SPECT study.

OBJECTIVE: Since brain perfusion abnormalities have been described by single-photon emission computed tomography in some autoimmune diseases, the aim of the present study was to evaluate the incidence of perfusion abnormalities by brain single-photon emission computed tomography in a group of coeliac disease patients, and to investigate whether gluten intake and associated autoimmune diseases may be considered risk factors in causing cerebral impairment. METHODS: Thirty-four adult coeliac patients (16 on a gluten-free diet and 18 on a gluten-containing diet, 18 (53%) with autoimmune diseases) underwent 99mTc-ethyl cysteinate dimer brain single-photon emission computed tomography and qualitative evaluation of brain perfusion was performed together with a semiquantitative estimation using the asymmetry index. Ten subjects on our database, matched for sex, age and ethnic group, who were proved normal by histology ofjejunal mucosa (four males and six females; median age 39 years, range 27-55 years), were included as control group. RESULTS: Twenty-four out of 34 patients (71%) showed brain single-photon emission computed tomography abnormalities confirmed by abnormal regional asymmetry index (>5%; range 5.8-18.5%). Topographic comparison of the brain areas showed that the more significant abnormalities were localised in frontal regions, and were significantly different from controls only in coeliac disease patients on unrestricted diet. The prevalence of single-photon emission computed tomography abnormalities was similar in coeliac disease patients with (74%) and without (69%) associated autoimmune disease. CONCLUSIONS: Abnormalities of brain perfusion seem common in coeliac disease. This phenomenon is similar to that previously described in other autoimmune diseases, but does not appear to be related to associated autoimmunity and, at least in the frontal region, may be improved by a gluten-free diet.

Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis.

PURPOSE: Brain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimoto's thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of 99mTc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent. METHODS: The diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent 99mTc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere--frontal, temporal, parietal and occipital--and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry. RESULTS: As assessed by visual examination, 99mTc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered. CONCLUSION: These results show the high prevalence of brain perfusion abnormalities in euthyroid HT. These abnormalities are similar to those observed in cases of severe Hashimoto's encephalopathy and may suggest a higher than expected involvement of CNS in thyroid autoimmune disease.

Frequency decomposition and compounding of ultrasound medical images with wavelet packets.

Ultrasound beams propagating in biological tissues undergo distortions due to local inhomogeneities of the acoustic parameters and the nonlinearity of the medium. The spectral analysis of the radio-frequency (RF) backscattered signals may yield important clinical information in the field of tissue characterization, as well as enhancing the detectability of tissue parenchymal diseases. In this paper, we propose a new tissue spectral imaging technique based on the wavelet packets (WP) decomposition. In a conventional ultrasound imaging system, the received echo-signals are generally decimated to generate a medical image, with a loss of information. With the proposed approach, all the RF data are processed to generate a set of frequency subband images. The ultrasound echo signals are simultaneously frequency decomposed and decimated, by using two quadrature mirror filters, followed by a dyadic subsampling. In addition, to enhance the lesion detectability and the image quality, we apply a nonlinear filter to reduce noise in each subband image. The proposed method requires simple additional signal processing and it can be implemented on any real-time imaging system. The frequency subband images, which are available simultaneously, can be either used in a multispectral display or summed up together to reduce speckle noise. To localize the different frequency response in the tissues, we propose a multifrequency display method where three different subband images, chosen among those available, are encoded as red, green, and blue intensities (RGB) to create a false-colored RGB image. According to the clinical application, different choices can evidence different spectral proprieties in the biological tissue under investigation. To enhance the lesion contrast in a grey-level image, one of the possible methods is the summation of the images obtained from narrow frequency subbands, according to the frequency compounding technique. We show that by adding the denoised subband images created with the WP decomposition, the contrast-to-noise ratio in two phantom images is largely increased.

Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: a retrospective single institution's study.

AIMS AND BACKGROUND: [corrected] The purpose of the study was to analyze the long-term follow-up of a single institution's experience with a regimen of concomitant carboplatin + 5-fluorouracil (CBDCA + 5-FU) infusion and radiotherapy. STUDY DESIGN: Fifty-eight patients with locally advanced squamous cell head and neck cancer treated with combined chemoradiotherapy between March 1990 and October 1998 were reviewed retrospectively. According to the TNM tumor staging, 6 patients had stage II, 21 stage III and 31 stage IV tumors. The chemotherapy regimen consisted of the combination of 5-FU and CBDCA, for a total of 3 cycles. Both drugs were given as 4-day continuous intravenous infusions during the first and fourth week of radiation therapy: 5-FU at 1000 mg/m2 per day and CBDCA at 75 mg/m2 per day. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 70 Gy. RESULTS: After the completion of chemotherapy and radiotherapy, 34 patients (58.6%) achieved clinical and radiological (computerized tomography and/or magnetic resonance imaging) complete remission, 15 patients (25.9%) partial remission >50%, 5 patients (8.6%) partial remission <50%, and 4 patients (6.8%) had no response. Toxicity was intensive but tolerable. After a median follow-up of 25 months, overall survival and recurrence-free survival estimated for the whole patient population was 52% at 3 years, and the median length of recurrence-free survival was 23 months. CONCLUSIONS: Our regimen combining standard single daily fraction radiation with the conventional dose of CBDCA and 5-FU was given without dose modification regardless of the severity of the adverse effects. It gave a clinical complete response at the primary site in 58.6% of patients. With a 52% projected 3-year overall survival, our series compares favorably with similar studies in the literature. Therefore, our results with concomitant CBDCA/5-FU infusion and radiotherapy are encouraging and suggest that CBDCA can be substituted for cisplatin with a good therapeutic index.

Phthalein derivatives as a new tool for selectivity in thymidylate synthase inhibition.

A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designed to specifically complement structural features of a bacterial form of thymidylate synthase (Lactobacillus casei, LcTS) versus the human TS (hTS) enzyme. The new compounds were screened for their activity and their specificity against TS enzymes from different species, namely, L. casei (LcTS), Pneumocystis carinii (PcTS), Cryptococcus neoformans (CnTS), and human thymidylate synthase (hTS). Apparent inhibition constants (Ki) for all the compounds against LcTS were determined, and inhibition factors (IF, ratio between the initial rates of the enzymatic reaction in the presence and absence of each inhibitor) against each of the four TS species were measured. A strong correlation was found between the two activity parameters, IF and Ki, and therefore the simpler IF was used as a screening factor in order to accelerate biological evaluation. Compounds 5b, 5c, 5ba, and 6bc showed substantial inhibition of LcTS while remaining largely inactive against hTS, illustrating for the first time remarkable species specificity among TSs. Due to sequence homology between the enzymes, several compounds also showed high activity and specificity for CnTS. In particular, 3-hydroxy-3-(3-chloro-4-hydroxyphenyl)-6-nitro-1H, 3H-naphtho[1,8-c,d]pyran-1-one (6bc) showed an IF < 0.04 for CnTS (Ki = 0.45 microM) while remaining inactive in the hTS assay at the maximum solubility concentration of the compound (200 microM). In cell culture assays most of the compounds were found to be noncytotoxic to human cell lines but were cytotoxic against several species of Gram-positive bacteria. These results are consistent with the enzymatic assays. Intriguingly, several compounds also had selective activity against Cr. neoformans in cell culture assay. In general, the most active and selective compounds against the Gram-positive bacteria were those designed and found in the enzyme assay to be specific for LcTS versus hTS. The original lead compound was least selective against most of the cell lines tested. To our knowledge these compounds are the first TS inhibitors selective for bacterial TS with respect to hTS.

Visualisation of a paraganglioma by technetium-99m-sestamibi scintigraphy.

A 68-yr-old woman presented to our observation with multinodular goiter and a contiguous right laterocervical mass. In spite of ultrasound, technetium and iodine scan, CT and fine-needle biopsy, the precise origin of the mass remained uncertain. On additional multi-phase sestamibi scan, the neck region showed an early high uptake rapidly decreasing over time in the laterocervical mass, and a persistent inhomogeneous distribution in the thyroid gland. This behavior suggested that the laterocervical mass could derive from an anatomical structure other than the thyroid. Surgical exploration established the extrathyroid nature of the laterocervical mass and the histological examination confirmed that it was a typical paraganglioma. This finding is in keeping with a recent report of positive sestamibi uptake in a cervical paraganglioma, although our case showed a more rapid kinetic. This tumor should be therefore taken into consideration in the differential interpretation of focal sestamibi uptake.

Dosimetry of Gamma Knife and linac-based radiosurgery using radiochromic and diode detectors.

In stereotactic radiosurgery the choice of appropriate detectors, whether for absolute or relative dosimetry, is very important due to the steep dose gradient and the incomplete lateral electronic equilibrium. For both linac-based and Leksell Gamma Knife radiosurgery units, we tested the use of calibrated radiochromic film to measure absolute doses and relative dose distributions. In addition a small diode was used to estimate the relative output factors. The data obtained using radiochromic and diode detectors were compared with measurements performed with other conventional methods of dosimetry, with calculated values by treatment planning systems and with data prestored in the treatment planning system supplied by the Leksell Gamma Knife (LGK) vendor. Two stereotactic radiosurgery techniques were considered: Leksell Gamma Knife (using gamma-rays from 60Co) and linac-based radiosurgery (LR) (6 MV x-rays). Different detectors were used for both relative and absolute dosimetry: relative output factors (OFs) were estimated by using radiochromic and radiographic films and a small diode; relative dose distributions in the axial and coronal planes of a spherical polystyrene phantom were measured using radiochromic film and calculated by two different treatment planning systems (TPSs). The absolute dose at the sphere centre was measured by radiochromic film and a small ionization chamber. An accurate selection of radiochromic film was made: samples of unexposed film showing a percentage standard deviation of less than 3% were used for relative dose profiles, and for absolute dose and OF evaluations this value was reduced to 1.5%. Moreover a proper calibration curve was made for each set of measurements. With regard to absolute doses, the results obtained with the ionization chamber are in good correlation with radiochromic film-generated data, for both LGK and LR, showing a dose difference of less than 1%. The output factor evaluations, performed using different methods, are in good agreement with a maximum difference of 1.5% for all field sizes considered (LGK and LR) except the 4 mm helmet used in the LGK unit. In this case, differences exist between diode and radiochromic film measurements and both detectors show data values larger than the prestored OF value of 0.80. Dose profiles measured by radiochromic film and calculated are in excellent agreement for both LGK and LR with a maximum deviation of less than 1.0 mm, when full widths of the dose profiles at 20%, 50%, 80% levels are considered. When external photon beams are used in stereotactic radiosurgery, the 'well selected' radiochromic films are very accurate detectors both for relative and absolute dosimetry. The experimental results, obtained using both radiochromic and diode detectors, show that the 4 mm helmet relative output factor could be underestimated.

Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS).

PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N-shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning.

Increased survival in brain metastatic patients treated with stereotactic radiotherapy, omega three fatty acids and bioflavonoids.

Stereotactic radiotherapy represents a method to effectively treat brain metastases with high precision and with high doses. Few acute toxicities are associated with stereotactic radiotherapy, however delayed reactions may occur and after six months, 20% of patients can develop radionecrosis. To avoid this adverse effect, in patients with metastases localized in critical brain areas, a supplementation of Omega three fatty acids and bioflavonoids has been used. At the end of 1997, we initiated a series of retrospective studies to test the efficacy of stereotactic radiotherapy on 405 patients, and the prognostic importance on survival of various variables among which this type of supplementation. From the comparison of various survival curves with the Cox multivariate analysis, it emerged that the patients using this supplementation had a decreased risk ratio and an improvement in survival time. A decreased number of radionecrosis was noted. We suggest their use as radioprotectors.

Design and characterization of a dynamic multileaf collimator.

The characteristics of a prototype computer-assisted dynamic multileaf collimator (DMLC), specifically designed for small-field conformal radiotherapy, were evaluated at the Istituto Nazionale Tumori of Milan. The collimating device consists of two opposing banks of 16 pairs of 8 cm thick, 3.6 mm wide tungsten leaves and allows shaping of a radiation field up to a size of 10 x 10 cm2 at the isocentre. The screening thickness of each leaf is 6.25 mm at the accelerator gantry isocentre. The leaves have a trapezoidal cross section and move along an arched path, thus providing a 'double focused' collimation system. The DMLC was installed on the head of a Varian Clinac 2100C linear accelerator. Mechanical and dosimetric evaluations were performed to test the stability of the mechanical isocentre and to determine leaf leakage, penumbra width, accuracy of leaf positions and uniformity of leaf speed. Displacement of the mechanical isocentre was less than 1 mm at all gantry angles. Standard radiographic films exposed to 6 MV x-ray radiation were used for dosimetric evaluations. Leakage between leaves was less than 2.5%, and leakage through abutted leaves was less than 5.5%. The penumbra width between 20% and 80% isodose at different positions of leaf banks was 2.7 mm in the direction of the leaf motion and 3.1 mm along the side of the leaf with a standard deviation of 0.2 mm in both directions. Accuracy in the positioning of the leaf was 0.3 mm, whereas the maximum repositioning error was less than 0.2 mm. Finally, during movement of the leaves at the maximum speed of 0.5 mm s(-1), the standard deviation of the leaf positioning error was 0.2 mm, proving an accurate uniformity of leaf speed.