Rulon Mayer

Clinical use of on-line portal imaging for daily patient treatment verification

Abstract Purpose: To determine the ease of use by clinical staff and reliability of an electronic portal imaging system and evaluate the potential to utilize on-line imaging to assess accuracy of daily patient treatment positioning in radiation therapy. Methods and Materials: A computer controlled fluorescent screen-mirror imaging system was used to acquire online portal images. A physician panel assessed on-line image quality relative to standard portal film. Clinical use of the imager was implemented through a protocol where images were obtained during the first six monitor units of external beam. The images were visually compared to a reference portal and patient setup was adjusted for errors exceeding 5 mm. Subsequent off-line analysis was utilized to give insight into the magnitude of clinical setup error in the visually accepted images. Results: Physician evaluation of on-line image quality with an initial 211 images found that 70% were comparable or superior to standard film portal images. Eighty percent of treatment fields fit completely within the on-line imaging area. Eight percent of on-line images were rejected due to poor image quality. Twelve percent of the daily treatment setups imaged required adjustment overall, but specific field types predictably required more frequent adjustment (pelvic and mantle fields). Off-line analysis of accepted images demonstrates that 18% of the final images had setup errors exceeding 5 mm. Conclusion: On-line imaging facilitated daily portal alignment and verification. Ease of use, almost instantaneous viewing and consistent ability to identify and locate anatomical landmarks imply the potential for on-line imaging to replace film based approaches. Retrospective analysis of daily images reveals that visual assessment of setup is not sufficient for eliminating localization errors. Further improvement is required with respect to detecting localization error and fully encompassing larger field sizes.

A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media

PURPOSE To describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. METHODS AND MATERIALS This technique uses the newly developed radiochromic dye medium (Gafchromic) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. We have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen antibodies. Individual tissues from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. RESULTS The absorbed dose distribution due to 90Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. The dose and spatial dose distribution were calculated assuming that the total 90Y activity is distributed uniformly throughout a half ellipsoid. The calculated spatial dose distributions for the half ellipsoids were similar to those observed from the dosimetry media that had been exposed to radioactivity contained in the tumors. CONCLUSION This method provides direct dose evaluation without elaborate summary calculations based on activity measurements from serial slices. The measured radiation dose actually indicates the dose rate at the time of animal sacrifice. Quantitative analysis of radiation emitted from the tissues is relatively fast, making it feasible to examine a number of tissues under a variety of conditions.

CT number distribution and its association with local control and as a marker of lung tumor response to radiation

An early noninvasive indicator of tumor response to therapy and the ability to predict clinical outcome may potentially enhance disease management. Currently, however, tumor response to therapy is often delayed, potentially compromising disease management. We examined the computed tomography (CT) number or Hounsfield unit distribution to follow lung tumor response to radiation treatment. To help interpret the results, we examined whether the CT number distribution follows a simple two-component model. The CT number distribution was derived from a CT-simulator for 11 patients with lung cancer before and after the initial radiation treatment (1-1.5 months, average 3,407 cGy). Clinical outcomes were followed in 8 patients who received 5,580-6,660 cGy. All patients were scanned serially, using identical radiation imaging parameters (voltage, current, scan time, and slice thickness) in a CT-simulator. The lung tumors were digitally contoured, and software windows were applied to avoid inclusion of lung tissue in the analysis. Histograms and statistical analysis of the CT numbers for the tumor were generated. Radiation-induced CT number or Hounsfield unit (HU) shifts exceeding a threshold (13 HU) in lung tumors were associated with (P=0.04) local control (> or = 10 months). Initial lung tumor size (below 100 cm3) was less well-associated with local control (P=0.26). The change in standard deviation of the CT numbers (derived from the more careful contouring and using software windows) induced by radiation treatment correlated with the change in average CT number (R2=0.71). The change in standard deviation did not correlate with a change in tumor volume (R2=0.02). Radiation treatments reduced the average CT number (P < 0.001). In summary, radiation reduces the CT number and this reduction may be associated with local control at 10 months. A two-component model is consistent with lung tumor number distribution and its response to radiation.

Direct measurement of intratumor dose-rate distributions in experimental xenografts treated with 90Y-labeled radioimmunotherapy

PURPOSE To measure, quantify, and evaluate the planar dose-rate distribution for human tumor xenografts implanted into mice that are treated with 90Y-labeled monoclonal antibodies or bispecific antibodies and 90Y-labeled haptens. METHODS AND MATERIALS Twenty-five LS174T human colon carcinoma tumors grown subcutaneously in nude mice were treated with 90Y by either directly labeled ZCE025 or bispecific ECA001-DBX antibody systems. A simple, quick technique using GAF radiochromic medium determined the dose-rate distribution in a plane passing through the tumor center. The dose-rate distribution is generated from exposure to activity situated in one-half of the tumor (0.045 to 0.83 g). RESULTS Planar dose-rate distributions were obtained from the tumor xenografts. Planar dose-rate histograms were computed along with the coefficients of variance and skewness of the distributions. The observed dose-rate distributions were quantitatively compared to those calculated for a uniformly distributed activity in a half-ellipsoid of the same volume and approximate shape as the tumor half. The observed dose-rate distributions were usually broader with a more positive coefficient of skewness than the dose-rate distributions calculated from the uniformly active half-ellipsoids. For 90Y, tumor shape plays an important role in determining the minimum tumor dose. For these tumors, the tumor minimum dose-rate is always observed along the edge, usually where the edge curvature is most convex. Larger tumors tended to have broader dose-rate distributions and more positive coefficients of skewness. Exceptions to this trend were associated with dose-rate maxima displaced from the central regions due to activity heterogeneity or tumor size greatly exceeding the range of emission. Calculations for dose rate from the conventional Medical Internal Radiation Dose (MIRD) formulation exceeded the average and minimum dose rate derived from radiochromic media. The coefficient of skewness became more positive for increasing time between injection and tumor excision, consistent with the activity evolving into a more uniform activity distribution. CONCLUSION Using radiochromic media to measure the spatial dose-rate distribution is a valuable method for comparing the dose-rate heterogeneity among experimental tumor xenografts in animals treated with radiolabeled antibodies. Tumor size (relative to the particle range) and changes in activity distribution radiolabeled antibodies. Tumor size (relative to the particle range) and changes in activity distribution affect the dose-rate distribution that are reflected by changes in the coefficients of skewness and variation of the dose-rate area histogram. The increase in coefficients of variation and skewness with tumor size and time results from the size of the 90Y beta particle penetration range that either exceeds or is comparable to the tumor dimensions. The minimum dose rate is more dependent, relative to the average and the maximum dose rates, on the curvature of the tumor surface.

Prediction of tumor response to experimental radioimmunotherapy with 90Y in nude mice

PURPOSE To identify those factors that predict variability in tumor response to 90Y-radioimmunotherapy based on measurement of incorporated activity and physical dimensions of individual tumors and to apply the concept of effective dose to radioimmunotherapy. METHODS AND MATERIALS Human colon carcinoma xenografts growing in nude mice were treated with anti-CEA antibodies labeled with 90Y directly or through a bispecific antibody/labeled hapten system. Tumor response was measured as the delay in growth to eight times the treatment volume. Noninvasive activity (based on bremsstrahlung radiation) and dimension measurements were made in these animals at several times after label injection. The following parameters were compared for their ability to predict individual tumor response: (a) injected activity, (b) injected activity times a factor based on average uptake as a function of volume, (c) in vivo activity per volume measured in each animal at a single time, (d) the integral over time of in vivo activity per volume in each animal, and (e) the minimum dose for each animal in a uniformly active ellipsoid whose total activity and dimensions varied over time the same as the tumor. RESULTS AND CONCLUSION After correcting for differences in injected activity, two parameters account for much of the variability in tumor response. One of these is the general trend of larger tumors to take up less activity per volume. Additional variability can be accounted for by the in vivo activity per volume measurements. The minimum dose as introduced here is likely to be useful in estimating the biologically effective dose delivered by each treatment.

Use of Bremsstrahlung radiation to monitor Y-90 tumor and whole body activities during experimental radioimmunotherapy in mice

Background. Large differences in uptake between tumors, even for the same size, frequently observed in clinical and experimental radioimmunotherapy (RAIT), make monitoring of uptake in individual tumors imperative in comparing protocols. 90Y, widely‐used for RAIT, emits no gamma radiation and absorption of the beta particle in tissue makes its detection unsuitable for in vivo monitoring. We tested whether bremsstrahlung radiation, produced when betas are decelerated by nuclei, could be used to monitor tumor uptake.

CT-simulator based brachytherapy planner: Seed localization and incorporation of biological considerations

Radiation dose prescription, interpretation, and planning can be problematic for brachytherapy due to high spatial heterogeneity, varying and various dose rates, absence of superimposed calculated isodose distributions onto affected tissues, and lack of dose volume histograms. A new treatment planner has been developed to reduce these limitations in brachytherapy planning. The PC-based planning system uses a CT-simulator to sequentially scan the patient to generate orthogonal images (to localize seed positions) and subsequently axially scan the patient. This sequential scanning procedure avoids using multiple independent patient scans, templates, external frames, or fiducial markers to register the reconstructed seed positions with patient contours. Dose is computed after assigning activity to (low dose rate) Ir192, linear Cs137, or I125 seeds or dwell times (high dose rate) to the Ir192 source. The planar isodose distribution is superimposed onto axial, coronal, or sagittal views of the tissues following image reconstruction. The treatment plan computes (1) direct and cumulative volume dose histograms for individual tissues, (2) the average, standard deviation, and coefficient of skewness of the dose distribution within individual tissues, (3) an average (over all tissue pixels) survival probability (S) and average survival dose DASD for a given radiation treatment, (4) normal tissue complication probability (NTCP) delivered to a given tissue. All four computed quantities account for dose heterogeneity. These estimates of the biological response to radiation from laboratory-based studies may help guide the evaluation of the prescribed low- or high-dose rate therapy in retrospective and prospective clinical studies at a number of treatment sites.

Clinical use of on-line portal imaging for daily patient treatment

PURPOSE To determine the ease of use by clinical staff and reliability of an electronic portal imaging system and evaluate the potential to utilize on-line imaging to assess accuracy of daily patient treatment positioning in radiation therapy. METHODS AND MATERIALS A computer controlled fluorescent screen-mirror imaging system was used to acquire on-line portal images. A physician panel assessed on-line image quality relative to standard portal film. Clinical use of the imager was implemented through a protocol where images were obtained during the first six monitor units of external beam. The images were visually compared to a reference portal and patient setup was adjusted for errors exceeding 5 mm. Subsequent off-line analysis was utilized to give insight into the magnitude of clinical setup error in the visually accepted images. RESULTS Physician evaluation of on-line image quality with an initial 211 images found that 70% were comparable or superior to standard film portal images. Eighty percent of treatment fields fit completely within the on-line imaging area. Eight percent of on-line images were rejected due to poor image quality. Twelve percent of the daily treatment setups imaged required adjustment overall, but specific field types predictably required more frequent adjustment (pelvic and mantle fields). Off-line analysis of accepted images demonstrates that 18% of the final images had setup errors exceeding 5 mm. CONCLUSION On-line imaging facilitated daily portal alignment and verification. Ease of use, almost instantaneous viewing and consistent ability to identify and locate anatomical landmarks imply the potential for on-line imaging to replace film based approaches. Retrospective analysis of daily images reveals that visual assessment of setup is not sufficient for eliminating localization errors. Further improvement is required with respect to detecting localization error and fully encompassing larger field sizes.

Focused neutron beam dose deposition profiles in tissue equivalent materials: a pilot study for BNCT

Boron Neutron Capture Therapy (BNCT) has been limited by the inability to direct neutrons toward the therapeutic target and away from sensitive normal tissues. The recently developed Kumakhov lens has focused a broad incident low energy neutron beam in air to a sub-mm spot. This study examines the radiation does distribution of a converging beam passing through tissue equivalent materials. A neutron beam exiting a focusing lens is directed toward a stack of thin radiochromic media sandwiched between plastic sheets. The depth dose and beam profile within the tissue equivalent materials are determined by optical scanning and image processing of the individual radiochromic media sheets, a polymer based dosimetry medium which darkens upon exposure to ionizing radiation. The alpha particle emission from boron is examined by substituting a plastic sheet with a 6Li enriched lithium carbonate sheet positioned at the focal plane. The information will help determine the feasibility of applying the focused neutron beam to BNCT for therapy.

Outpatient interstitial thermoradiotherapy.

Hyperthermia enhances the cytocidal effect of ionizing radiation. Several pilot studies demonstrated that the combination of interstitial hyperthermia and interstitial radiotherapy (interstitial thermoradiotherapy) is safe and effective. However, these studies mainly utilized low dose rate brachytherapy, and therefore, required hospitalization. With the availability of median or high dose rate brachytherapy devices, we piloted a study to evaluate the feasibility, toxicity and efficacy of interstitial thermoradiotherapy performed in an outpatient setting.