PubMed Health⌕ Search

Biomedical subjects

X Allen Li

Publications and source records attributed to X Allen Li.

At least 19 recordsLinked to original sources
PubMed2006

Halftime for repair of sublethal damage in normal bladder and rectum: an analysis of clinical data from cervix brachytherapy.

The halftime for repair of sub-lethal damage is an important radiobiological parameter in analysing radiation responses and in designing new treatments involving different dose rates. This work is to resolve an inconsistency existing in the repair halftime for the bladder and rectum, two of the most dose limiting critical structures for pelvic irradiation. Both long (1.5-2 h) and short (0.3-1 h) repair halftimes have been reported previously. In this work, by reconciling clinical data from cervical brachytherapy of different dose rates and by introducing a sparing factor to consider the dose sparing occurring for critical structures, we have estimated that the most likely value of the repair halftime for bladder and rectum is short, 0.2-0.4 h if assuming alpha/beta = 2-4 Gy. The present analysis does not support the long repair halftimes reported previously for the bladder and rectum and for other normal structures.

Brachytherapy↗
PubMed2006

Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma.

PURPOSE: The purpose of this study is to evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused with planning computed tomography (CT) on tumor localization, which guided intensity-modulated radiotherapy (IMRT) of patients with head-and-neck carcinoma. METHODS AND MATERIALS: From October 2002 through April 2005, we performed FDG-PET/CT guided IMRT for 28 patients with head-and-neck carcinoma. Patients were immobilized with face masks that were attached with five fiducial markers. FDG-PET and planning CT scans were performed on the same flattop table in one session and were then fused. Target volumes and critical organs were contoured, and IMRT plans were generated based on the fused images. RESULTS: All 28 patients had abnormal increased uptake in FDG-PET/CT scans. PET/CT resulted in CT-based staging changes in 16 of 28 (57%) patients. PET/CT fusions were successfully performed and were found to be accurate with the use of the two commercial planning systems. Volume analysis revealed that the PET/CT-based gross target volumes (GTVs) were significantly different from those contoured from the CT scans alone in 14 of 16 patients. In addition, 16 of 28 patients who were followed for more than 6 months did not have any evidence of locoregional recurrence in the median time of 17 months. CONCLUSION: Fused images were found to be useful to delineate GTV required in IMRT planning. PET/CT should be considered for both initial staging and treatment planning in patients with head-and-neck carcinoma.

Adult↗
PubMed2006

An estimation of radiobiologic parameters from clinical outcomes for radiation treatment planning of brain tumor.

PURPOSE: To estimate a plausible set of radiobiologic parameters such as alpha, alpha/beta values, from clinical outcomes for biologically based radiation treatment planning of brain tumors. METHODS AND MATERIALS: Linear-quadratic (LQ) formalism and the concept of equivalent uniform dose were used to analyze a series of published clinical data for malignant gliomas involving different forms of radiation therapy. RESULTS: A plausible set of LQ parameters was obtained for gliomas: alpha = 0.06 +/- 0.05 Gy(-1), alpha/beta = 10.0 +/- 15.1 Gy, the tumor cell doubling time T(d) = 50 +/- 30 days, with the repair half-time of 0.5 h. The present estimated biologic parameters can reasonably predict the effectiveness of most of the recently reported clinical results employing either single or combined radiation therapy modalities. Different LQ parameters between Grade 3 and Grade 4 astrocytomas were found, implying the radiosensitivity for different grade tumors may be different. Smaller alpha, beta from in vivo was observed, indicating lower radiosensitivity occurred in vivo as compared with in vitro. CONCLUSIONS: A plausible set of radiobiologic parameters for gliomas was estimated based on clinical data. These parameters can reasonably predict most of the clinical results. They may be used to design new treatment fractionation schemes and to evaluate and optimize treatment plans.

Algorithms↗
PubMed2006

Technical and dosimetric aspects of respiratory gating using a pressure-sensor motion monitoring system.

This work introduces a gating technique that uses 4DCT to determine gating parameters and to plan gated treatment, and employs a Siemens linear accelerator to deliver the gated treatment. Because of technology incompatibility, the 4DCT scanner (LightSpeed, GE) and the Siemens accelerator require two different motion-monitoring systems. The motion monitoring system (AZ-773V, Anzai Med.) used for the gated delivery utilizes a pressure sensor to detect the external respiratory motion (pressure change) in real time. Another system (RPM, Varian) used for the 4DCT scanner (LightSpeed, GE) is based on an infrared camera to detect motion of external markers. These two motion monitoring systems (RPM and Anzai systems) were found to correlate well with each other. The depth doses and profile measured for gated delivery (with a duty cycle of 25% or 50%) were found to agree within 1.0% with those measured for ungated delivery, indicating that gating did not significantly alter beam characteristics. The measurement verified also that the MU linearity and beam output remained unchanged (within 0.3%). A practical method of using 4DCT to plan a gated treatment was developed. The duty cycle for either phase or amplitude gating can be determined based on 4DCT with consideration of set-up error and delivery efficiency. The close-loop measurement involving the entire gating process (imaging, planning, and delivery) showed that the measured isodose distributions agreed with those intended, validating the accuracy and reliability of the gating technique. Based these observations, we conclude that the gating technique introduced in this work, integrating Siemens linear accelerator and Anzai pressure sensor device with GE/Varian RPM 4DCT, is reliable and effective, and it can be used clinically to account for respiratory motion during radiation therapy.

Imaging, Three-Dimensional↗
PubMed2005

Using a photon phase-space source for convolution/superposition dose calculations in radiation therapy.

For a given linac design, the dosimetric characteristics of a photon beam are determined uniquely by the energy and radial distributions of the electron beam striking the x-ray target. However, in the usual commissioning of a beam from measured data, a large number of variables can be independently tuned, making it difficult to derive a unique and self-consistent beam model. For example, the measured dosimetric penumbra in water may be attributed in various proportions to the lateral secondary electron range, the focal spot size and the transmission through the tips of a non-divergent collimator; the head-scatter component in the tails of the transverse profiles may not be easy to resolve from phantom scatter and head leakage; and the head-scatter tails corresponding to a certain extra-focal source model may not agree self-consistently with in-air output factors measured on the central axis. To reduce the number of adjustable variables in beam modelling, we replace the focal and extra-focal sources with a single phase-space plane scored just above the highest adjustable collimator in a EGS/BEAM simulation of the linac. The phase-space plane is then used as photon source in a stochastic convolution/superposition dose engine. A photon sampled from the uncollimated phase-space plane is first propagated through an arbitrary collimator arrangement and then interacted in the simulation phantom. Energy deposition kernel rays are then randomly issued from the interaction points and dose is deposited along these rays. The electrons in the phase-space file are used to account for electron contamination. 6 MV and 18 MV photon beams from an Elekta SL linac are used as representative examples. Except for small corrections for monitor backscatter and collimator forward scatter for large field sizes (<0.5% with <20 x 20 cm2 field size), we found that the use of a single phase-space photon source provides accurate and self-consistent results for both relative and absolute dose calculations.

Algorithms↗
PubMed2005

Simultaneous integrated intensity-modulated radiotherapy boost for locally advanced gynecological cancer: radiobiological and dosimetric considerations.

PURPOSE: Whole-pelvis irradiation (WPI) followed by a boost to the tumor site is the standard of practice for the radiotherapeutic management of locally advanced gynecologic cancers. The boost is frequently administered by use of brachytherapy or, occasionally, external-beam radiotherapy (EBRT) when brachytherapy does not provide sufficient coverage because of the size of the tumor or the geometry of the patient. In this work, we propose using an intensity-modulated radiotherapy (IMRT) simultaneous integrated boost (SIB), which is a single-phase process, to replace the conventional two-phase process involving WPI plus a boost. Radiobiological modeling is used to design appropriate regimens for the IMRT SIB. To demonstrate feasibility, a dosimetric study is carried out on an example patient. METHODS AND MATERIALS: The standard linear-quadratic (LQ) model is used to calculate the biologically effective dose (BED) and equivalent uniform dose (EUD). A series of regimens that are biologically equivalent to those conventional two-phase treatments is calculated for the proposed SIB. A commercial inverse planning system (Corvus) was used to generate IMRT SIB plans for a sample patient case that used the newly designed fractionations. The dose-volume histogram (DVH) and EUD of both the target and normal structures for conventional treatments and the SIB are compared. A sparing factor was introduced to characterize the sparing of normal structures. RESULTS: Fractionation regimes that are equivalent to the conventional treatments and are suitable for the IMRT SIB are deduced. For example, a SIB plan with 25 x 3.1 Gy (77.5 Gy) to a tumor is equivalent to a conventional treatment of EBRT of 45 Gy to the whole pelvis in 25 fractions plus a high-dose rate (HDR) brachytherapy boost with 30 Gy in 5 fractions. The normal tissue BED is found to be lower for the SIB plan than for the whole-pelvis plus HDR scheme when a sparing factor for the critical structures is considered. This finding suggests that the IMRT SIB has a better therapeutic ratio. Three IMRT SIB plans with 25 x 1.8 Gy to the pelvic nodes and 25 x 2.4 Gy (60 Gy), 25 x 2.8 Gy (70 Gy), and 25 x 3.2 Gy (80 Gy) to the tumor site were generated for the example patient case. The target coverage ranged from 94% to 95.5%. The sparing of bladder and rectum is significantly improved with the 60 to 70 Gy SIB treatments, as compared with the conventional treatments. The proposed SIB treatment can reduce the treatment time to 5 weeks. CONCLUSIONS: An IMRT simultaneous integrated boost to replace the conventional two-phase treatments (whole pelvic irradiation followed by brachytherapy or EBRT boost) is radiobiologically and dosimetricaly feasible for locally advanced gynecological cancers that may not be amenable to brachytherapy for anatomic or medical reasons. In addition to its shorter treatment time, the proposed IMRT SIB can provide significant sparing to normal structures, which offers potential for dose escalation. Issues such as organ motion and changing anatomy as tumor responds still must be addressed.

Female↗
PubMed2005

Dosimetric advantages of IMRT simultaneous integrated boost for high-risk prostate cancer.

PURPOSE: A sequential two-phase process, initial and boost irradiation, is the common practice for the radiotherapy management of high-risk prostate cancer. In this work, we explore the feasibility of using intensity modulated radiation therapy (IMRT) simultaneous integrated boost (SIB), a single-phase process, to simultaneously deliver high dose to the prostate and lower dose to the pelvic nodes. In addition, we introduce the concept of voxel-equivalent dose for the comparison of treatment plans. METHODS AND MATERIALS: The SIB is designed to deliver the same dose (e.g., 45 Gy, 25 x 1.8 Gy) as the conventional method to the pelvic nodes and to deliver higher doses to prostate in the same 25 fractions (i.e., hypofractionation). The equivalent uniform dose (EUD) was used to determine suitable SIB fractionations that deliver the biologically equivalent doses to prostate. For tumor, the EUD was estimated based on the linear quadratic (LQ) model. The most recent LQ parameters derived from clinical data for prostate cancer were used. The sensitivity of LQ parameters was evaluated. The EUD for normal tissue was computed based on the widely used Lyman model. To be able to consider biologic effectiveness spatially (e.g., voxel by voxel), we propose a new concept, termed the voxel-equivalent dose (VED). The calculation of VED was similar to that for EUD, except that it was done within a voxel. To demonstrate dosimetric feasibility and advantages of the proposed IMRT SIB, we have performed a retrospective planning study on selected patient cases using commercial IMRT and three-dimensional (3D) planning systems. Four treatment scenarios were considered: (1) the conventional 3D plan for initial whole-pelvic irradiation and subsequent conventional 3D boost plan for prostate gland, (2) the conventional 3D plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, (3) IMRT plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, and (4) IMRT SIB. EUDs and VED-based dose-volume histograms for prostate, pelvic nodes, small bowel, rectum, bladder, and other tissue for all 4 scenarios were compared. RESULTS: A series of equivalent hypofractionation regimens suitable for the IMRT SIB were obtained for high-risk prostate cancer. For example, the conventional treatment regimen of 42 x 1.8 Gy (EUD = 75.4 Gy) would be equivalent to a SIB regimen of 25 x 2.54 Gy. From the comparison of 3D VED dose distributions and dose-volume histograms between the SIB and the conventional two-phase irradiation, we found that the SIB offers better or equivalent dose conformity to prostate and pelvic nodes and better sparing to the critical structures. For example, for the 4 treatment scenarios with a prostate EUD of 75.4 Gy, the corresponding rectal EUDs are 67.1 (3D + 3D), 65.6 Gy (3D + IMRT), 63.7 Gy (IMRT + IMRT), and 62.0 Gy (SIB). CONCLUSIONS: A new IMRT simultaneous integrated boost strategy that irradiates prostate via hypofractionation while irradiating pelvic nodes with the conventional fractionation is proposed for high-risk prostate cancer. Compared to the conventional two-phase treatment, the proposed SIB technique offers potential advantages, including better sparing of critical structures, more efficient delivery, shorter treatment duration, and better biologic effectiveness.

Dose Fractionation, Radiation↗
PubMed2005

Impact of tumor repopulation on radiotherapy planning.

PURPOSE: Biologic/functional imaging (e.g., fluorodeoxyglucose/3'-deoxy-3'-fluorothymidine-positron emission tomography) is promising to provide information on tumor cell repopulation. Such information is important in the design of biologically conformal radiotherapy for cancer. The questions remaining unclear are whether it is necessary to escalate the dose to the regions with rapid cell repopulation in the tumor target and, if so, by how much. The purpose of this work was to address these questions using radiobiologic modeling. METHODS AND MATERIALS: The generalized linear-quadratic model, extended to account for the effect of clonogenic cell repopulation, was used to calculate the cell-killing efficiency of radiotherapy. The standard Poisson tumor control probability (TCP) model was used to bridge cell killing to treatment outcome. Prostate cancer was chosen as the example for this study. In situ measurements of prostate cancer patients have shown that the potential doubling time of tumor cells has a large variation, ranging from 15 to 170 days. On the basis of the linear-quadratic and TCP parameters (alpha = 0.14 Gy(-1), alpha/beta = 3.1 Gy, and the number of clonogens K = 10(6)-10(7) cells) determined in earlier studies, we evaluated the influence of tumor cell repopulation during protracted treatment courses on treatment outcome. The dose escalations, which can be used to combat aggressive cell repopulation in regions with different doubling times (15-170 days) and sizes (5, 10, 15, and 40 cm(3) of a 40-cm(3) tumor), were calculated for commonly practiced radiotherapy modalities. The influence of linear-quadratic parameters on this calculation was also considered. RESULTS: The impact of tumor cell repopulation on TCP and the corresponding dose escalation required to account for this impact were investigated for both external beam radiotherapy and permanent implantation. The results indicated that for regions with aggressive tumor cell growth, dose escalation is necessary to compensate for the repopulation effect. For example, for tumors with an effective doubling time changing from 42 days to 15 days, the prescription dose of external beam radiotherapy needs to be increased from 75.6 to 81 Gy to maintain a target TCP of 80% for intermediate-risk prostate cancer. For (125)I implants, dose escalation from 152 to 160 Gy is required for the same target TCP. These data were calculated on the basis of an alpha/beta ratio of 3.1 Gy. Greater dose escalations are required if the alpha/beta ratio is 1.5 Gy (e.g., 88 Gy for external beam radiotherapy or 180 Gy for (125)I implantation for the same treatment outcome). Our study results showed that it is important to cover the entire tumor volume, including all aggressive spots, with the desired prescription dose, especially for low-dose-rate brachytherapy. CONCLUSION: Dose escalation is necessary to offset the accelerated tumor cell repopulation during prolonged treatment courses. This study provides a preliminary estimate of the dose escalation for prostate cancer based on the in situ measurements of potential doubling time and radiobiologic models. The proposed dose prescriptions are technically feasible for clinical trials.

Brachytherapy↗
PubMed2005

Improving patient-specific dosimetry for intravascular brachytherapy.

PURPOSE: Accurate patient-specific dosimetry in intravascular brachytherapy (IVBT) is generally difficult due to the extremely high-dose gradient, complexity of treatment device, and patient-specific geometry (e.g., calcification, stent, curvature, movement of target). The purpose of this study is to analyze quantitatively and systematically the dose effects of calcification, stent, guidewire, and source curvature on clinical dosimetry in an IVBT procedure, and propose a method that can be used to assess these effects in routine clinical practice. METHODS AND MATERIALS: Monte Carlo techniques were used to calculate 3-D dose distribution in both homogeneous and inhomogeneous media for three most commonly used IVBT sources: (90)Sr beta (Novoste), (192)Ir gamma (Cordis/Best), and (32)P beta (Guidant). Dosimetric perturbations in the presence of metallic stents, calcified plaques, metallic guide wires, and source curvature were studied for situations commonly encountered in the clinic. The importance of each of these perturbations and their practical influence on patient-specific dosimetry were analyzed. Factors (plaque, stent, guidewire, and curvature) that may be used to correct/reduce these perturbations were introduced to prevent dosimetric cold spots during IVBT. Practical methods of using these correction factors are proposed. RESULTS: Dose perturbations are significant due to the presence of source curvature, metallic stents, calcified plaques, and metallic guide wires, especially for beta sources. These perturbations can be as high as 30% under normal clinical conditions, although they can be much higher in extreme situations. Empirical relationships of plaque factor with the thickness of calcified plaque, stent factor with stent metallic surface area, guidewire with guidewire thickness, and curvature factor with the bending angle are derived. These relationships are found to be useful in improving clinical dose accuracy in IVBT treatment planning or dose evaluation after treatment. CONCLUSIONS: Significant dose perturbations due to the presence of source curvature, metallic stents, calcified plaques, and guide wires have been found in IVBT for in-stent restenosis. Because it has been reported that, with the current prescriptions for IVBT, higher doses consistently improve treatment outcomes, the empirical method derived from this work can be used to assess cold spots dosimetrically, thus improving patient-specific dosimetry for IVBT.

Blood Vessel Prosthesis Implantation↗
PubMed2005

Dose perturbations due to contrast medium and air in mammosite treatment: an experimental and Monte Carlo study.

In the management of early breast cancer, a partial breast irradiation technique called MammoSite (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated in recent years. In MammoSite, a balloon implanted at the surgical cavity during tumor excision is filled with a radio-opaque solution, and radiation is delivered via a high dose rate brachytherapy source situated at the center of the balloon. Frequently air may be introduced during placement of the balloon and/or injection of the contrast solution into the balloon. The purpose of this work is to quantify as well as to understand dose perturbations due to the presence of a high-Z contrast medium and/or an air bubble with measurements and Monte Carlo calculations. In addition, the measured dose distribution is compared with that obtained from a commercial treatment planning system (Nucletron PLATO system). For a balloon diameter of 42 mm, the dose variation as a function of distance from the balloon surface is measured for various concentrations of a radio-opaque solution (in the range 5%-25% by volume) with a small volume parallel plate ion chamber and a micro-diode detector placed perpendicular to the balloon axis. Monte Carlo simulations are performed to provide a basic understanding of the interaction mechanism and the magnitude of dose perturbation at the interface near balloon surface. Our results show that the radio-opaque concentration produces dose perturbation up to 6%. The dose perturbation occurs mostly within the distances <1 mm from the balloon surface. The Plato system that does not include heterogeneity correction may be sufficient for dose planning at distances > or = 10 mm from the balloon surface for the iodine concentrations used in the MammoSite procedures. The dose enhancement effect near the balloon surface (<1 mm) due to the higher iodine concentration is not correctly predicted by the Plato system. The dose near the balloon surface may be increased by 0.5% per cm3 of air. Monte Carlo simulation suggests that the interface effect (enhanced dose near surface) is primarily due to Compton electrons of short range (<0.5 mm). For more accurate dosimetry in MammoSite delivery, the dose perturbation due to the presence of a radio-opaque contrast medium and air bubbles should be considered in a brachytherapy planning system.

Artifacts↗
PubMed2004

Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy.

Ongoing clinical trials designed to explore the use of extracranial stereotactic radiosurgery (ESR) for different tumour sites use large doses per fraction (15, 20, 30 Gy or even larger). The question of whether the linear-quadratic (LQ) model is appropriate to describe radiation response for such large fraction doses has been raised and has not been answered definitively. It has been proposed that mechanism-based models, such as the lethal-potentially lethal (LPL) model, could be more appropriate for such large fraction/acute doses. However, such models are not well characterized with clinical data and they are generally not easy to use. The purpose of this work is to modify the LQ model to more accurately describe radiation response for high fraction/acute doses. A new parameter is introduced in the modified LQ (MLQ) model. The new parameter introduced is characterized based both on in vitro cell survival data of several human tumour cell lines and in vivo animal iso-effect curves. The MLQ model produces a better fit to the iso-effect data than the LQ model. For a high single dose irradiation, the prediction of the MLQ is consistent with that from the LPL model. Unlike the LPL model, the MLQ model retains the simplicity of the LQ model and uses the well-characterized alpha and beta parameters. This work indicates that the standard LQ model can lead to erroneous results when used to calculate iso-effects with large fraction doses, such as those used for ESR. We present a solution to this problem.

Animals↗
PubMed2004

Comparison of in vitro and in vivo alpha/beta ratios for prostate cancer.

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy.

Alpha Particles↗
PubMed2004

Simultaneous integrated boost for breast cancer using IMRT: a radiobiological and treatment planning study.

PURPOSE: The purpose of this work is to explore the possibility of using intensity-modulated radiation therapy (IMRT) to deliver the boost dose to the tumor bed simultaneously with the whole-breast IMRT to reduce the radiation treatment time by 1-2 weeks. METHODS AND MATERIALS: The biologically effective dose (BED) for different treatments was calculated using the linear-quadratic (LQ) model with parameters previously derived for breast cancer from clinical data (alpha/beta = 10Gy, alpha = 0.3Gy(-1)). A potential doubling time of 15 days (from in vitro measurements) for breast cancer and a generic alpha/beta ratio of 3 Gy for normal tissues were used. A series of regimens that use IMRT as initial treatment and an IMRT simultaneous integrated boost (SIB) were derived using biologic equivalence to conventional schedules. Possible treatment plans with IMRT SIB to the tumor bed were generated for 2 selected breast patients, 1 with a shallow tumor and 1 with a deep-seated tumor. Plans with a simultaneous integrated electron boost were also generated for comparison. Dosimetric merits of these plans were evaluated based on dose volume histograms. RESULTS: A commonly used conventional treatment of 45 Gy (1.8 Gy x 25) to the whole breast and then a boost of 20 Gy (2 Gy x 10) is biologically equivalent to an alternative plan of 1.8 Gy x 25 to the whole breast with a 2.4 Gy x 25 SIB to the tumor bed. The new regime reduces treatment time from 7 to 5 weeks. For the patient with a deep-seated tumor, the IMRT plans reduce the volume of the breast that receives high doses (compared with the conventional photon boost plan) and provides good coverage of the target volumes. CONCLUSION: It is biologically and dosimetrically feasible to reduce the overall treatment time for breast radiotherapy by using an IMRT simultaneous integrated boost. For selected patient groups, IMRT plans with a new regimen can be equal to or better than conventional plans.

Breast Neoplasms↗
PubMed2004

Radiation absorbed dose distribution in a patient treated with yttrium-90 microspheres for hepatocellular carcinoma.

We have implemented a three-dimensional dose calculation technique accounting for dose inhomogeneity within the liver and tumor of a patient treated with 90Y microspheres. Single-photon emission computed tomography (SPECT) images were used to derive the activity distribution within liver. A Monte Carlo calculation was performed to create a voxel dose kernel for the 90Y source. The activity distribution was convolved with the voxel dose kernel to obtain the three-dimensional (3D) radiation absorbed dose distribution. An automated technique was developed to accurately register the computed tomography (CT) and SPECT scans in order to display the 3D dose distribution on the CT scans. In addition, dose-volume histograms were generated to fully analyze the tumor and liver doses. The calculated dose-volume histogram indicated that although the patient was treated to the nominal whole liver dose of 110 Gy, only 16% of the liver and 83% of the tumor received a dose higher than 110 Gy. The mean tumor and liver doses were 163 and 58 Gy, respectively.

Body Burden↗
PubMed2003

The low alpha/beta ratio for prostate cancer: what does the clinical outcome of HDR brachytherapy tell us?

PURPOSE: Accumulating evidence demonstrates that prostate cancer has a low alpha/beta ratio. However, several challenging issues have been raised from previous studies, including the biologic equivalence between external beam radiotherapy (EBRT) and brachytherapy, the effect of relative biologic effectiveness (RBE) for permanent implantation, and the systematic uncertainties of multi-institutional and multi-modality clinical data. The purpose of this study is to address these issues by reexamining a reported clinical outcome of high-dose-rate (HDR) brachytherapy and to confirm the low alpha/beta ratio for prostate cancer. METHODS AND MATERIALS: The generalized linear-quadratic (LQ) model with considerations of sublethal damage repair and clonogen repopulation was used to calculate the cell-killing efficiency of radiotherapy treatments for prostate cancer. Standard models of tumor cure based on Poisson statistics were used to bridge cell killing to treatment outcome. The data collected in a clinical trial using EBRT plus HDR brachytherapy boost for prostate cancer at William Beaumont Hospital (WBH) were reanalyzed. A 4-year post-treatment time endpoint was chosen as compared to the 3-year endpoint used in the previous study because of better maturity and stability of the data. The least chi-square method was employed to fit the clinical data to estimate the LQ parameters as well as their confidence intervals. The number of clonogens for prostate tumors derived in a separate study was used as a constraint for the data modeling to improve the confidence level. RESULTS: Our analysis demonstrates that only relationships among the LQ parameters, not their definitive and unique values, can be derived from the WBH data set alone. This is due to the large statistical uncertainties, i.e., the small numbers of sampled patients. By combining with the results obtained with the clinical data from Memorial Sloan-Kettering Cancer Center (MSKCC), a new set of LQ parameters (alpha = 0.14 +/- 0.05 Gy(-1), alpha/beta = 3.1(-1.6)(+2.6) Gy) was obtained from the current analysis of the WBH data without dealing with data from permanent implants. The results are consistent with a previous study based on the biologic equivalence between EBRT and permanent implants with a consideration of tumor repopulation. This set of LQ parameters provides a consistent interpretation of clinical data currently available for prostate cancer. CONCLUSIONS: This study provides further evidence to support that prostate cancer has a low alpha/beta ratio of about 3.1 Gy. This study shows that the RBE effect in permanent implantation may not be clinically significant for prostate cancer. The consistency found between this analysis and the previous reported study supports the general biologic equivalence between EBRT and brachytherapy treatments for prostate cancer. The low alpha/beta ratio opens the door to search for more effective radiotherapeutic approaches for prostate cancer, e.g., hypofractionation radiotherapy.

Brachytherapy↗
PubMed2003

Analysis of a large number of clinical studies for breast cancer radiotherapy: estimation of radiobiological parameters for treatment planning.

Numerous studies of early-stage breast cancer treated with breast conserving surgery (BCS) and radiotherapy (RT) have been published in recent years. Both external beam radiotherapy (EBRT) and/or brachytherapy (BT) with different fractionation schemes are currently used. The present RT practice is largely based on empirical experience and it lacks a reliable modelling tool to compare different RT modalities or to design new treatment strategies. The purpose of this work is to derive a plausible set of radiobiological parameters that can be used for RT treatment planning. The derivation is based on existing clinical data and is consistent with the analysis of a large number of published clinical studies on early-stage breast cancer. A large number of published clinical studies on the treatment of early breast cancer with BCS plus RT (including whole breast EBRT with or without a boost to the tumour bed, whole breast EBRT alone, brachytherapy alone) and RT alone are compiled and analysed. The linear quadratic (LQ) model is used in the analysis. Three of these clinical studies are selected to derive a plausible set of LQ parameters. The potential doubling time is set a priori in the derivation according to in vitro measurements from the literature. The impact of considering lower or higher T(pot) is investigated. The effects of inhomogeneous dose distributions are considered using clinically representative dose volume histograms. The derived LQ parameters are used to compare a large number of clinical studies using different regimes (e.g., RT modality and/or different fractionation schemes with different prescribed dose) in order to validate their applicability. The values of the equivalent uniform dose (EUD) and biologically effective dose (BED) are used as a common metric to compare the biological effectiveness of each treatment regime. We have obtained a plausible set of radiobiological parameters for breast cancer: alpha = 0.3 Gy(-1), alpha/beta = 10 Gy and sub-lethal damage repair time T(rep) = 1 h (mono-exponential behaviour is assumed). This set of parameters is consistent with in vitro experiments and with previously reported analyses. Using this set of parameters, we have found that most of the studies, using BCS plus whole breast RT and a boost to the tumour bed, have EUDs ranging from 60-70 Gy. No correlation is found between BED and the local recurrence rate. The treatments of BCS plus brachytherapy alone have a wide range of EUD (30-50 Gy), which is significantly lower than the treatments with whole breast EBRT plus a boost of the tumour bed. The studies with different fractionation schemes for whole breast EBRT also show a significant variation of EUD. Carefully designed clinical studies with large numbers of patients are required to determine clinically the relative effectiveness of these treatment variations. The derived LQ parameter set based on clinical data is consistent with in vitro experiments and previous studies. As demonstrated in the present work, these radiobiological parameters can be potentially useful in radiotherapy treatment planning for early breast cancer, e.g., in comparing biological effectiveness of different radiotherapy modalities, different fractionation schemes and in designing new treatment strategies.

Brachytherapy↗