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Biomedical subjects

F M Buffa

Publications and source records attributed to F M Buffa.

11 recordsLinked to original sources
PubMed2006

A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone.

PURPOSE: We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of (186)Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). METHODS: Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of (186)Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. RESULTS: Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq (186)Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. CONCLUSION: We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach.

Aged↗
PubMed2003

Multicellular dosimetry in voxel geometry for targeted radionuclide therapy.

A software package to investigate absorbed doses and dose-rates at the cellular and multicellular scale has been developed that considers two- and three-dimensional activity distributions and makes use of analytical representations of the point-dose kernels for (131)I, (32)P, and (90)Y. This software allows cell assemblies to be simulated by definition of the number, size, and geometry of cells and their nuclei, and radionuclide uptake can be specified to occur within the nucleus, the cytoplasm, at the membrane, or within the extracellular space. The software has been validated at a cellular scale by comparison with results obtained using spherical geometry, as found in the literature. At a multicellular scale, comparisons were made with a Monte Carlo simulation in voxel geometry. The software has been designed to work within a user-defined voxel geometry. This geometry is useful not only to simulate complex cell assemblies and realistic heterogeneous radionuclide distributions, but will also allow the use of histological and autoradiographic data. Absorbed dose distributions for a single cell calculated using this code varied significantly with activity localization within the cell, and to a lesser extent, with the cellular geometry. At a multicellular level, a two-dimensional heterogeneous activity distribution inferred from a two-dimensional image of a slice throughout a spheroid was used to calculate a dose-rate distribution. This resulted in a heterogeneous dose-rate delivery even for longer-range radionuclides such as (90)Y and (32)P.

Absorption↗
PubMed2002

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.

Bone Neoplasms↗
PubMed2001

Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Carcinoma, Squamous Cell↗
PubMed2001

Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.

PURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values. CONCLUSIONS: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.

Adenocarcinoma↗
PubMed2001

Dosimetric features of linac head and phantom scattered radiation outside the clinical photon beam: experimental measurements and comparison with treatment planning system calculations.

BACKGROUND AND PURPOSE: Dosimetric measurements and treatment planning system (TPS) calculations in the region outside the clinical photon beams have been investigated. The aim was to estimate the calculation accuracy of a specific TPS in areas that are becoming increasingly relevant with the advent of new technologies, such as, for example, intensity modulation radiation therapy. MATERIALS AND METHODS: Measurements were performed on two different linacs to obtain, separately, the head scatter (electrons and photons), the transmission below the jaws and the phantom scatter outside the primary beam for different photon energies, distances from the field edge and field sizes. Calculations with a commercial TPS (Helax TMS) were then obtained and compared with these measurements. RESULTS: In general, reasonable agreement between calculations and measurements was obtained (1-2%), especially for photon scattering (head and phantom). Nevertheless, some discrepancies were found in the electron contamination computation, due probably to the approximations and assumptions made in the TPS calculation algorithm. CONCLUSIONS: The analyzed TPS presented good results, but for some particular clinical cases and moreover for advanced techniques such as intensity modulated radiation therapy, the calculation behaviour with respect to measurements and patient dose delivery should be carefully evaluated.

Algorithms↗
PubMed2001

Quantifying effects of lead shielding in electron beams: a Monte Carlo study.

Lead shielding in contact with the patient's skin is often encountered in radiotherapy with electron beams. The influence of the lead shielding on dose distributions in the patient cannot fully be assessed using modern treatment planning systems. In this work the problem of quantifying the effect of lead shielding on dose distributions is addressed. Monte Carlo dose calculations were performed in a half-blocked water phantom shielded by lead, using a realistic model for the fluence of an electron linear accelerator. Electron beam energies of 6-20 MeV and lead thicknesses of 1-7 mm are used for 10 x 10 cm2 and 5 x 5 cm2 fields. The perturbation of the particle fluence and dose distributions in water introduced by the lead shielding is quantified. The effect of oblique electron beams on the dose perturbation is shown. A fictitious clinical example, the shielding of an eye in electron beam treatment, is used to demonstrate the usefulness of Monte Carlo based treatment planning algorithms that can incorporate the effects of lead shielding.

Algorithms↗
PubMed2000

Comparative analysis of dose volume histogram reduction algorithms for normal tissue complication probability calculations.

A model for estimating radiotherapy treatment outcome through the probability of damage to normal tissue and the probability of tumour control is a useful tool for treatment plan optimization, dose escalation strategies and other currently used procedures in radiation oncology. Normal tissue complication estimation (NTCP) is here analysed from the point of view of the reliability and internal consistency of the most popular model. Five different dose volume histogram (DVH) reduction algorithms, applied to the Lyman model for NTCP calculation. were analysed and compared. The study was carried out for sets of parameters corresponding to quite different expected dose-response relationships. In particular, we discussed the dependence of the models on the parameters and on the dose bin size in the DVH. The sensitivity of the different reduction schemes to dose inhomogeneities was analysed, using a set of simple DVHs representing typical situations of radiation therapy routine. Significant differences were substantiated between the various reduction methods regarding the sensitivity to the degree of irradiation homogeneity, to the model parameters and to the dose bin size. Structural aspects of the reduction formalism allowed an explanation for these differences. This work shows that DVH reduction for NTCP calculation has still to be considered as a very delicate field and used with extreme care, especially for clinical applications, at least until the actual formulations are tuned against strong clinical data.

Algorithms↗
PubMed2000

Monte Carlo dose calculations and radiobiological modelling: analysis of the effect of the statistical noise of the dose distribution on the probability of tumour control.

The aim of this work is to investigate the influence of the statistical fluctuations of Monte Carlo (MC) dose distributions on the dose volume histograms (DVHs) and radiobiological models, in particular the Poisson model for tumour control probability (tcp). The MC matrix is characterized by a mean dose in each scoring voxel, d, and a statistical error on the mean dose, sigma(d); whilst the quantities d and sigma(d) depend on many statistical and physical parameters, here we consider only their dependence on the phantom voxel size and the number of histories from the radiation source. Dose distributions from high-energy photon beams have been analysed. It has been found that the DVH broadens when increasing the statistical noise of the dose distribution, and the tcp calculation systematically underestimates the real tumour control value, defined here as the value of tumour control when the statistical error of the dose distribution tends to zero. When increasing the number of energy deposition events, either by increasing the voxel dimensions or increasing the number of histories from the source, the DVH broadening decreases and tcp converges to the 'correct' value. It is shown that the underestimation of the tcp due to the noise in the dose distribution depends on the degree of heterogeneity of the radiobiological parameters over the population; in particular this error decreases with increasing the biological heterogeneity, whereas it becomes significant in the hypothesis of a radiosensitivity assay for single patients, or for subgroups of patients. It has been found, for example, that when the voxel dimension is changed from a cube with sides of 0.5 cm to a cube with sides of 0.25 cm (with a fixed number of histories of 10(8) from the source), the systematic error in the tcp calculation is about 75% in the homogeneous hypothesis, and it decreases to a minimum value of about 15% in a case of high radiobiological heterogeneity. The possibility of using the error on the tcp to decide how many histories to run for a given voxel size is also discussed.

Computer Simulation↗
PubMed2000

An analysis of the relationship between radiosensitivity and volume effects in tumor control probability modeling.

The dependence of local tumor control probability (tcp) on tumor volume is analyzed and discussed with the help of radiobiological modeling; in particular the impact of possible correlations between mean tumor radiosensitivity and tumor dimensions on the tcp volume dependence is explored. The linear-quadratic Poissonian tumor control probability (tcp) model was modified to account for the possible dependence of clonogenic cell density and radiosensitivity parameters on tumor volume; then the original and modified versions of the model were fitted to published clinical and laboratory tumor control data. These different versions of the tcp model often fitted tumor control data equally well, because of the high degree of correlation between the parameters. Nevertheless the results were very different from a physical point of view and we suggest that sometimes it is possible to choose between equally good fits on the basis of physical considerations. Possible links between the volume dependence of the mean radiosensitivity and the degree of tumor hypoxia were also analyzed through a comparison of the results of the tcp fit to published measurements of oxygen tension in tumors.

Animals↗