Cheng-Shie Wuu

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

Factors predicting for postimplantation urinary retention after permanent prostate brachytherapy

PURPOSE Urinary retention requiring catheterization is a known complication among prostate cancer patients treated with permanent interstitial radioactive seed implantation. However, the factors associated with this complication are not well known. This study was conducted to determine these factors. METHODS AND MATERIALS Ninety-one consecutive prostate cancer patients treated with permanent interstitial implantation at our institution from 1996 to 1999 were evaluated. All patients underwent pre-implant ultrasound and postimplant CT volume studies. Isotopes used were (125)I (54 patients) or (103)Pd (37 patients). Twenty-three patients were treated with a combination of 45 Gy of external beam radiation therapy as well as seed implantation, of which only 3 patients were treated with (125)I. Mean pretreatment prostate ultrasound volume was 35.4 cc (range, 10.0-70.2 cc). The mean planning ultrasound target volume (PUTV) was 39.6 cc (range, 16.1-74.5 cc), whereas the mean posttreatment CT target volume was 55.0 cc (range, 20.2-116 cc). Patient records were reviewed to determine which patients required urinary catheterization for relief of urinary obstruction. The following factors were analyzed as predictors for urinary retention: clinical stage; Gleason score; prostate-specific antigen; external beam radiation therapy; hormone therapy; pre-implant urinary symptoms (asymptomatic/nocturia x 1 vs. more significant urinary symptoms); pretreatment ultrasound prostate volume; PUTV; PUTV within the 125%, 150%, 200%, 250%, 300% isodose lines; postimplant CT volume within the 125%, 150%, 200%, 250%, 300% isodose lines; D90; D80; D50; ratio of post-CT volume to the PUTV; the absolute change in volume between the CT volume and PUTV; number of needles used; activity per seed; and the total activity of the implant. Statistical analyses using logistic regression and chi2 were performed. RESULTS Eleven of 91 (12%) became obstructed. Significant factors predicting for urinary retention were the total number of needles used (p < 0.038); the pretreatment ultrasound prostate volume (p < 0.048); the PUTV (p < 0.02); and the posttreatment CT volume (p < 0.021). Two of 51 patients (3.9%) requiring 33 or fewer needles (median) experienced obstruction vs. 9 of 40 (22.5%) requiring more than 33 (p < 0.007). If the pretreatment ultrasound prostate volume was 35 cc or less (median), 3 of 43 (7%) vs. 8 of 36 (22%) with a volume greater than 35 cc experienced obstruction (p < 0.051). CONCLUSION The number of needles required (perhaps related to trauma to the prostate) and the prostate volumes were significant factors predicting for urinary retention after permanent prostate seed implantation.

Spectrum-Analysis and Neural Networks for Imaging to Detect and Treat Prostate Cancer

Conventional B-mode ultrasound currently is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy to treat prostate cancer. Yet B-mode images do not adequately display cancerous lesions of the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of radiofrequency (rf) echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. This method of tissue-type imaging utilizes nonlinear classifiers, such as neural networks, to classify tissue based on values of spectral parameter and clinical variables. Two- and three-dimensional images based on these methods demonstrate potential for guiding prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional images are being generated in real time in ultrasound scanners used for real-time biopsy guidance and have been incorporated into commercial dosimetry software used for brachytherapy planning. Three-dimensional renderings show promise for depicting locations and volumes of cancer foci for disease evaluation to assist staging and treatment planning, and potentially for registration or fusion with CT images for targeting external-beam radiotherapy.

Microdosimetric evaluation of relative biological effectiveness for 103Pd, 125I, 241Am, and 192Ir brachytherapy sources

PURPOSE To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates. METHODS AND MATERIALS The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). RESULTS Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir. CONCLUSIONS These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Dosimetry study of Re-188 liquid balloon for intravascular brachytherapy using polymer gel dosimeters and laser-beam optical CT scanner.

Angioplasty balloons inflated with a solution of the beta-emitter Re-188 have been used for intravascular brachytherapy to prevent restenosis. Coronary stents are in extensive clinical use for the treatment of de novo atherosclerotic stenoses. In this study, the effect of an interposed stent on the dose distribution has been measured for Re-188 balloon sources using the proprietary BANG polymer gel dosimeters and He-Ne laser-beam optical CT scanner. In polymer gels, after ionizing radiation is absorbed, free-radical chain-polymerization of soluble acrylic monomers occurs to form an insoluble polymer. The BANG polymer gel dosimeters used in these measurements allow high resolution, precise, and accurate three-dimensional determination of dosimetry from a given source. Re-188 liquid balloons, with or without an interposed metallic stent, were positioned inside thin walled tubes placed in such a polymer dosimeter to deliver a prescribed dose (e.g., 15 Gy at 0.5 mm). After removing the balloon source, each irradiated sample was mounted in the optical scanner for scanning, utilizing a single compressed He-Ne laser beam and a single photodiode. In the absence of a stent, doses at points along the balloon axis, at radial distance 0.5 mm from the balloon surface and at least 2.5 mm from the balloon ends, are within 90% of the maximum dose. This uniformity of axial dose is independent of the balloon diameter and length. Dose rate and dose uniformity for intravascular brachytherapy with Re-188 balloon are altered by the presence of stent. The dose reduction by the stent is rather constant (13%-15%) at different radial distances. However, dose inhomogeneity caused by the stent decreases rapidly with radial distance.

Three-dimensional dose verification for intensity modulated radiation therapy using optical CT based polymer gel dosimetry

Dose distributions generated from intensity-modulated-radiation-therapy (IMRT) treatment planning present high dose gradient regions in the boundaries between the target and the surrounding critical organs. Dose accuracy in these areas can be critical, and may affect the treatment. With the increasing use of IMRT in radiotherapy, there is an increased need for a dosimeter that allows for accurate determination of three-dimensional (3D) dose distributions with high spatial resolution. In this study, polymer gel dosimetry and an optical CT scanner have been employed to implement 3D dose verification for IMRT. A plastic cylinder of 17 cm diameter and 12 cm height, filled with BANG3 polymer gels (MGS Research, Inc., Madison, CT) and modified to optimal dose-response characteristics, was used for IMRT dose verification. The cylindrical gel phantom was immersed in a 24 x 24 x 20 cm water tank for an IMRT irradiation. The irradiated gel sample was then scanned with an optical CT scanner (MGS Research Inc., Madison, CT) utilizing a single He-Ne laser beam and a single photodiode detector. Similar to the x-ray CT process, filtered back-projection was used to reconstruct the 3D dose distribution. The dose distributions measured from the gel were compared with those from the IMRT treatment planning system. For comparative dosimetry, a solid water phantom of 24 x 24 x 20 cm, having the same geometry as the water tank for the gel phantom, was used for EDR2 film and ion chamber measurements. Root mean square (rms) deviations for both dose difference and distance-to-agreement (DTA) were used in three-dimensional analysis of the dose distribution comparison between treatment planning calculations and the gel measurement. Comparison of planar dose distributions among gel dosimeter, film, and the treatment planning system showed that the isodose lines were in good agreement on selected planes in axial, coronal, and sagittal orientations. Absolute point-dose verification was performed with ion chamber measurements at four different points, varying from 48% to 110% of the prescribed dose. The measured and calculated doses were found to agree to within 4.2% at all measurement points. For the comparison between the gel measurement and treatment planning calculations, rms deviations were 2%-6% for dose difference and 1-3 mm for DTA, at 60%-110% doses levels. The results from this study show that optical CT based polymer gel dosimetry has the potential to provide a high resolution, accurate, three-dimensional tool for IMRT dose distribution verification.

A field size specific backscatter correction algorithm for accurate EPID dosimetry.

PURPOSE Portal dose images acquired with an amorphous silicon electronic portal imaging device (EPID) suffer from artifacts related to backscattered radiation. The backscatter signal varies as a function of field size (FS) and location on the EPID. Most current portal dosimetry algorithms fail to account for the FS dependence. The ramifications of this omission are investigated and solutions for correcting the measured dose images for FS specific backscatter are proposed. METHODS A series of open field dose images were obtained for field sizes ranging from 2×2 to 30×40cm2. Each image was analyzed to determine the amount of backscatter present. Two methods to account for the relationship between FS and backscatter are offered. These include the use of discrete FS specific correction matrices and the use of a single generalized equation. The efficacy of each approach was tested on the clinical dosimetric images for ten patients, 49 treatment fields. The fields were evaluated to determine whether there was an improvement in the dosimetric result over the commercial vendors current algorithm. RESULTS It was found that backscatter manifests itself as an asymmetry in the measured signal primarily in the inplane direction. The maximum error is approximately 3.6% for 10×10 and 12.5×12.5cm2 field sizes. The asymmetry decreased with increasing FS to approximately 0.6% for fields larger than 30×30cm2. The dosimetric comparison between the measured and predicted dose images was significantly improved (p⪡.001) when a FS specific backscatter correction was applied. The average percentage of points passing a 2%, 2 mm gamma criteria increased from 90.6% to between 96.7% and 97.2% after the proposed methods were employed. CONCLUSIONS The error observed in a measured portal dose image depends on how much its FS differs from the 30×40cm2 calibration conditions. The proposed methods for correcting for FS specific backscatter effectively improved the ability of the EPID to perform dosimetric measurements. Correcting for FS specific backscatter is important for accurate EPID dosimetry and can be carried out using the methods presented within this investigation.

Determining optimal gel sensitivity in optical CT scanning of gel dosimeters.

A method for determining the gel sensitivity that is necessary for obtaining optimal image contrast in optical CT scanning of gel dosimeters is presented. The effective dynamic range of the OCTOPUS-ONE research scanner (MGS Research, Inc., Madison, CT) is analyzed. Optical density increments for selected straight-line paths across a gel cylinder to be scanned are calculated based on the optical properties of the polymer gel and the dose distribution from a commercial treatment planning system (Cadplan, Varian Corporation, Palo Alto, CA). Maximum optical density increment across the entire gel is obtained by searching the gel cylinder over a set of transverse planes at different rotational angles. The application of this quantity as a criterion for optimizing the quality of the optical CT scanning is demonstrated through dose verification of two representative treatment plans. When the MU dependence of the dose distribution for a treatment plan is linear, as is the case for static field irradiation, it is possible to scale the treatment plan such that the intensity variation of the signals received by the photodetector spans its entire dynamic range. For treatment plans that are possibly nonlinear, IMRT plans, for example, modification of the sensitivity of the gel material is necessary for the high-dose signals to be collected at a certain signal-to-noise ratio. Results obtained using the optimized CT scanning approach are compared with those from the treatment planning system and the film measurement.

Improved biochemical control and clinical disease-free survival with intraoperative versus preoperative preplanning for transperineal interstitial permanent prostate brachytherapy

PURPOSEWe hypothesized that intraoperative preplanning for transperineal interstitial permanent prostate brachytherapy may yield better prostate cancer control than preoperative preplanning. We tested this hypothesis by comparing treatment outcomes of patients who underwent implantation using these two preplanning methods. PATIENTS AND METHODSWe analyzed the data of 135 consecutive patients with localized prostate cancer treated from 1996 to 2001 with transperineal interstitial permanent prostate brachytherapy ± preimplantation hormonal therapy: 42 received preoperative preplanning (group 1), and 93 underwent intraoperative preplanning (group 2). Biochemical status was assessed using two failure definitions: American Society for Therapeutic Radiology and Oncology (ASTRO) (three consecutive rises in prostate-specific antigen level) and Houston (prostate-specific antigen level ≥ current nadir + 2 ng/mL). Clinical disease-free survival and postimplantation dosimetry were also examined. RESULTSAll disease control outcomes were superior for group 2. The 4-year ASTRO biochemical no evidence of disease rate was 80% for group 1 versus 94% for group 2. The 4-year Houston biochemical no evidence of disease rate was 82% for group 1 versus 96% for group 2. The 4-year clinical disease-free survival rate was 87% for group 1 versus 99% for group 2. Preplanning method (preoperative versus intraoperative) remained predictive of disease control outcomes in multivariate analyses with the covariates of pretreatment prostate-specific antigen level, Gleason score, clinical stage, and case sequence number (proxy for brachytherapist experience and “stage migration”). Dosimetric prostate coverage was superior for group 2. The mean percentage of the prescription dose delivered to 90% of the prostate volume (%D90) was 75% for group 1 versus 90% for group 2. A %D90 ≥ 70% predicted for improved disease control; fewer group 1 than 2 patients met this dosimetric criterion (55% versus 87%). DISCUSSIONIntraoperative preplanning yielded superior disease control outcomes in this analysis, likely due at least in part to improved dosimetric prostate coverage with this method. Although not mandatory for obtaining high prostate brachy-therapy efficacy, intraoperative preplanning nevertheless may offer an excellent means of improving dosimetric prostate coverage and therefore disease control outcomes.

Ultrasonic spectrum-analysis and neural-network classification as a basis for ultrasonic imaging to target brachytherapy of prostate cancer

Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy of prostate cancer. Yet B-mode images do not allow adequate visualization of cancerous lesions of the prostate. Ultrasonic tissue-typing imaging based on spectrum analysis of radiofrequency echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. Tissue typing based on radiofrequency spectrum analysis uses nonlinear methods, such as neural networks, to classify tissue by using spectral-parameter and clinical-variable values. Two- and three-dimensional images based on these methods show potential for improving the guidance of prostate biopsies and the targeting of radiotherapy of prostate cancer. Two-dimensional images have been imported into instrumentation for real-time biopsy guidance and into commercial dose-planning software for brachytherapy planning. Three-dimensional renderings seem to be capable of depicting locations and volumes of cancer foci.