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Objective: To determine the rectal tolerance for developing Grade 2 radiation proctitis after 125I prostate implantation based on the rectal dose-volume histogram., Methods and Materials: Two hundred twelve patients with T1-T2 prostate cancer underwent 125I implantation without external beam irradiation. One month after the procedure, all patients underwent CT-based postimplant dosimetry (3-mm abutting slices). The rectal volumes, defined by an inner and outer wall, were determined from 9 mm above the seminal vesicles to 9 mm below the prostate apex. All doses were calculated by TG43 formalism. The prostate prescription dose was 160 Gy. A dose response analysis was undertaken for volumes of rectal tissue receiving a given dose. Dose levels examined were 80 Gy, 100 Gy, 120 Gy, 140 Gy, 160 Gy, 180 Gy, 200 Gy, 220 Gy, and 240 Gy. Grade 2 proctitis was defined as rectal bleeding occurring at least once a week for a minimum period of one month. The risk of proctitis was calculated using actuarial methods. For each dose level, a critical volume cutpoint was chosen to define a low and high volume group of patients. The cutpoint was determined based on two goals: minimizing thep value and finding a < or =5% risk of proctitis in the low volume group. Patients were followed from 12 to 61 months (median: 28 months) after implantation., Results: Twenty-two patients developed Grade 2 proctitis: 14% within the first year, 72% between the first and second year, and 14% during the third year after the implant date. After the third year postimplantation, no cases of proctitis were reported. Proctitis was found to be significantly volume dependent for a given dose. The prescription dose (160 Gy) delivered to < or =1.3 cc of rectal tissue resulted in a 5% rate of proctitis at 5 years vs. 18% for volumes >1.3 cc (p = 0.001). Similar results were found for all doses examined. As the rectal volume receiving the prescription dose (160 Gy) increased, so did the proctitis rate: 0% for < or =0.8 cc, 7% for >0.8-1.3 cc, 8% for >1.3-1.8 cc, 24% for >1.8-2.3 cc, and 25.5% for >2.3cc (p = 0.002)., Conclusions: Rectal dose-volume histogram analysis is a practical and predictive method of assessing the risk of developing Grade 2 proctitis after 125I prostate implantation. Delivered dose should be kept below defined rectal volume thresholds to minimize this risk. This information can allow one to decrease rectal morbidity by modifying prostate implant technique.

Objective: An analysis of CT-based dosimetry was performed to assess the efficacy of the real time method of prostate implantation, explore the relationship of various dose descriptions and determine implant factors affecting outcome., Methods and Materials: Between 7/95 and 8/99, 297 patients underwent (125)I implants for T1-T2 prostate cancer and had CT-based dosimetry performed (TG43 formalism). Dosimetry was performed 1 month postimplant. Using a dose-volume histogram, doses delivered to 100%, 95%, 90%, and 80% of the prostate (D100, D95, D90, D80, respectively) as well as percentages of the gland receiving 240 Gy, 160 Gy, 140 Gy (V240, V160, V140, respectively) were reported. Correlations between the various dose parameters and D90 were generated. The effect of the number of seeds implanted, seeds/volume, prostate volume, experience as assessed by time (8/01/99-date of implant), ultrasound probe (mechanical sector vs. dual phased electronic), and the ratio of the CT dosimetry prostate volume/ultrasound implant volume (CT/US vol) were analyzed., Results: The median D100, D95, D90, and D80 values were 10,200 cGy, 15,655 cGy, 17,578 cGy, and 19,873 cGy, respectively. The median V240, V160, and V140 were 56%, 94%, and 98%, respectively. Correlations of dose descriptions found a close relationship of D95, D80, V240, V160, and V140 with D90 with r values of 0.928, 0.973, 0.911, 0.816, and 0.733, respectively. D100 correlated poorly with D90 (r = 0.099). Using a stepwise regression analysis, CT/US vol ratio, prostate volume, and seed number were the only significant factors affecting D90 with CT/US vol ratio having the greatest effect. The dual-phased electronic probe was associated with fewer D90 values of less than 140 Gy (2%) compared to the mechanical sector probe (14%) (p = 0.02)., Conclusion: CT-based dosimetry results reveal the real-time implant technique to be an effective method of prostate implantation. Factors associated with more precise implantation, such as decreased postimplant edema, new technology, and increased number of seeds will lead to higher D90 values.

Purpose: To achieve more uniform dose distributions in breast cancer treatment using multiple sets of multi-leaf collimator (MLC) defined fields. Dose uniformity for many breast cancer patients can be significantly improved by using two or more sets of portals and the "hot" regions of a traditional treatment can be significantly reduced., Methods and Materials: Patients for breast cancer treatment are immobilized with alpha cradle in the traditional arm-up position and have a CT scan in the treatment position. The target volume is delineated on the 5-mm thick CT slices that are obtained from the lower neck to well below the breast target volume. Medial and lateral tangential fields at conventional gantry angles are designed with the aid of digitally reconstructed radiographs (DRRs). The MLC, without collimator rotation, is used to shape the field to spare as much lung as possible. The wedges and relative weights of the beams are optimized to provide the best dose uniformity. For the patients with large dose inhomogeneity, a second set of fields is designed. The weight of the original set of fields is reduced (usually to approximately 90%) so that the "original hot" regions receive the prescription dose; the second set of fields delivers a supplemental dose to the "cold" region, typically approximately 10% of the total dose. The second set of fields has the same beam parameters but "treat" only the part of breast tissue that is "cool." Presently, the design of the reduced field is an iterative process. The process can be extended to more than two sets of portals to obtain the desired dose uniformity., Results: With 3D planning and multiple MLC fields, dose uniformity in the treatment of breast patients was improved from 7%-22% to approximately 7%-15%. The volume receiving these high doses decreased significantly and shifted from the lung to the target. By keeping the gantry angles and wedges the same for the multiple fields, treatments can be delivered quickly and reliably. The internal mammary nodes (IM) can also be treated without including significant amount of lung or heart in the field., Conclusion: Dose uniformity can be significantly improved by using this intensity modulation technique to treat certain breast patients. With these static MLC fields creating the intensity modulation, the dose uniformity to the breast can be significantly improved and the hot region in lung reduced. There is no increase in setup complexity. The small increase in treatment time is insignificant.

Purpose: Combined brachytherapy of the prostate and external beam irradiation (EBRT) of the prostate and seminal vesicles (SV) is becoming a popular treatment for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV in patients undergoing this treatment was performed to determine the dose distribution to the SV and the adequacy of this treatment in patients with potential SV involvement., Methods and Materials: Twenty-five consecutive patients were treated with a Pd-103 implant of the prostate alone and 45 Gy of EBRT to the prostate and SV. Attempts were not made to implant the SV but seeds were routinely placed at the junction of the prostate and SV. All patients underwent CT-based postimplant dosimetric analysis 1 month after implantation. As part of this analysis, DVH were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 6-mm-thick volumes identified as SV1, SV2, SV3, SV4, and SV5 starting from the junction of the prostate and SV and extending distally. DVH were also generated for these structures. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH)., Results: The median volumes in cc of the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 34.33, 9.75, 2.7, 3.48, 2.92, 3.18, and 1.96 respectively. The SVT contained from 0-9 seeds (median 2). There was little dose delivered to the SVT and SV volumes from the implanted prostate. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 8615 cGy, 675 cGy, 3100 cGy, 1329 cGy, 553 cGy, 246 cGy, and 67 cGy, respectively. The dose delivered to the prostate covered small percentages of SV. The percents of SV volumes covered by the prostate D90 were 11, 35, 3.3, 0, 0, and 0 for SVT, SV1, SV2, SV3, SV4, and SV5, respectively., Conclusions: DVH analysis of the SV reveals that dose generated from an implanted prostate contributes little to the SV. Those patients at high risk for SV involvement may be undertreated with combined EBRT to prophylactic doses and prostate implantation.

Purpose: Brain tumors can be advantageously treated with electron over photon radiation, by exploiting the rapid fall-off in dose with depth. This advantage could be further enhanced by utilizing multiple electron beams. However, in some beam configurations, wedged dose profiles would be necessary for the dose uniformity. Unlike photons, shaped pieces of material placed in electron beam severely degrade the energy, give additional scattering and, therefore, are suboptimal. The purpose of this study was to create wedged electron fields, using intensity modulation. The combination of electron wedges enables a more uniform coverage of brain tumors with a reduced dose to normal tissue., Methods and Materials: Intensity modulation was performed for 10 to 50 MeV electrons using a narrow scanning elementary beam of a racetrack Microtron accelerator, delivering radiation pulses with coordinates and intensities prescribed by a custom scan matrix. Dispensing more pulses (or longer pulses) within the field to increase the local dose, one can sharpen the penumbra at depth and generate wedged dose distributions of arbitrary angle as well as many other desired profiles. We modulated the electron beams, measured dose distributions using film in an anthropomorphic phantom, and compared the results with conventional techniques., Results: Intensity modulation of electron beams decreases the 50-90% penumbra at depth by 40% and increases the flatness by 80%. Wedged profiles at depth can be created for any angle up to about 70 degrees, depending on the beam energy. Multiple modulated electron beams give smaller 20-70% but larger 70-100% isodose regions than photon beams., Conclusions: Electron beams can improve dose distributions in brain compared to the same number of photon beams, reducing the 20-70% isodoses region in normal tissue by 30%. Intensity modulation significantly improves the dose distribution from combined electron beams providing a sharper penumbra, better conformity, and reduced margin.

Purpose: To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room., Methods and Materials: Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile., Results: Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within +/-5% for all beam energies used in this study., Conclusions: Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and/or the field size.

Purpose: There may be radiobiological advantages in administering stereotaxic radiation treatment in multiple fractions instead of by a single irradiation. However, a larger planning target volume may be required for fractionated stereotaxic radiotherapy than for a single session treatment, if decreased geometrical precision and increased setup uncertainty are associated with multiple-fraction treatments. This factor may partially offset the radiobiological gain. The purpose of this study is to estimate the potential therapeutic gain of fractionated treatments for brain tumors, and to assess the effect of increased setup uncertainty on the potential gain., Methods and Materials: The concept of biologically effective dose (BED), based on the linear quadratic (LQ) model, was used to quantify the therapeutic efficacy of the respective treatment schema. Therapeutic gain (TG) was defined as the ratio of tumor BEDs, for multiple fractions and single treatment, respectively, for the same normal brain BED. To include the effect of increased planning volume in fractionated treatment, a power-law relationship was assumed for the volume dependence of prescription dose, and the TG was recalculated using the "volume-adjusted" doses., Results: The therapeutic gain for fractionated treatment increases with fraction number, and is smaller for larger single treatment doses. For example, in going from 1 to 10 fractions, the TG is 1.40, 1.32, or 1.27 for single treatment dose of 20, 30, or 40 Gy, respectively. Also, the TG is more significant for the initial few fractions. The benefit of fractionation is diminished if larger planning volume is needed for multiple fraction treatments. For example, the above TG are reduced to 1.19, 1.11, or 1.06, if a 2 cm planning target volume in single fraction treatment is enlarged to 2.3 cm in fractionated treatment., Conclusion: Consideration of the therapeutic gain with fractionation should include estimates of setup uncertainty for multiple-fraction treatments, relative to that of single fraction radiosurgery.

Purpose: The acute morbidity of doses of 64.8-75.6 Gy and preliminary observations of late complications and tumor response using 3-dimensional conformal radiation therapy in carcinoma of the prostate are assessed., Methods and Materials: 123 patients (Stage A2-12, B1-17, B2-43, C-51) were irradiated to the prostate and seminal vesicles using a 3-dimensional conformal radiation therapy technique. The median follow-up time was 15.2 months. The minimum tumor dose was 64.8-66.6 Gy in 49 patients, 70.2 Gy in 46, and 75.6 Gy in 28. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading system., Results: This technique of 3-dimensional conformal radiation therapy was well-tolerated with minimal acute morbidity. Only 32% of patients had grade 2 or 3 acute morbidity requiring short-term medication for relief of urinary symptoms or diarrhea. Only one patient (0.8%) has so far developed a severe (grade 4) late complication. Serum prostate specific antigen concentrations normalized in 67% of patients (64/96) within 1-14 months (median 4.5 months) after treatment and were progressively decreasing at last measurement in an additional 22% (21/96). Abnormal rising prostate specific antigen levels were observed in 15 patients, 11 of whom have already developed other evidence of relapsing disease., Conclusion: Acute toxicity for the doses tested with this 3-dimensional conformal radiation therapy technique is reduced compared to traditional treatment techniques, and the initial tumor response as assessed by prostate specific antigen measurement is highly encouraging with prostate specific antigen levels returning to normal in the majority of patients. Based on these results, a further increase of the dose to 81 Gy has been implemented in accordance with the schema of an ongoing Phase I dose-escalation study.

We have used a mouse model to study spinal cord injury following single doses (12 to 75 Gy) of radiation. The spinal cord (T9,10-L4,5) of C3Hf/Sed//Kam mice was irradiated and response graded using four levels of neurological change. Findings were: (a) the doses required to paralyze 50% of animals (ED50) were 19.79, 20.77, and 21.85 Gy for mild, partial, and complete paralysis, respectively, as measured 200-360 days after radiation. (b) Most damage was progressive but it was not necessarily so; after doses up to 28 Gy recovery was occasionally seen. (c) Latency depended on the dose and the level of damage. Following doses around the ED50, paralysis occurred between 180 to 300 days. (d) There were significant fluctuations in the dose-latency relationship at doses less than 35 Gy. Latency may be not a reliable endpoint to compare biological effects of radiation in this dose range. (e) The radiosensitivity of mouse spinal cord was similar to that reported for rats. (f) Histologically, demyelination was the dominant lesion in the paralyzed animals. We conclude that the mouse is a good animal model to study radiation damage to the spinal cord, at least when a 2.2 cm length is irradiated.