Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.

Ultrasound field calculation in a water-soft tissue medium.

An efficient numerical approximation for ultrasound field calculation in a two or three layer water-soft tissue medium is presented. It is extended from a method developed previously in a homogeneous medium. The emphasis of this study is to examine the conditions that are required for this approximation. Criteria are given for achieving an appropriate accuracy, which is verified by comparing it with the Rayleigh integral.

Ultrasound image fusion for external beam radiotherapy for prostate cancer.

PURPOSE: To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determine (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real-time imaging. METHODS AND MATERIALS: During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique. RESULTS: The transrectal ultrasound probe enabled real-time prostate imaging. The lateral field size can be reduced to 6.08 x 5.68 cm2 +/- 0.62 x 0.48 cm2 from the standard 8 x 8 cm2 field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field is 1.75 cm2 +/- 0.85 cm2. CONCLUSION: The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.

Design of an ultrasonic therapy system for breast cancer treatment.

This paper describes the design of a novel ultrasonic therapy system dedicated to the breast cancer treatment and the theoretical investigation of the heating characteristics of the system. The applicator is a cylinder comprised of a stack of rings. Each ring has up to 48 transducers mounted on the inside of the ring and directed towards the centre. The transducers operate in one of two frequency bands (1.8-2.8 MHz and 4.3-40.8 MHz), arranged alternately in each ring. During treatment the patient is positioned in prone position, with the breast immersed in water and surrounded by this array. This design was modelled and optimized by 3-D simulations for a variety of treatment conditions. The simulated results demonstrate that the system has an excellent capability to achieve and maintain a temperature distribution (41.5-44 degrees C) in a quadrant to a whole breast. Initial experiments using a single ring of transducers has been performed to verify the power deposition calculation.

Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours.

Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worth of study, especially since a positive interaction between these modalities is found in laboratory models.

Coumarin chemical dosimeter for radiation therapy.

Aqueous coumarin was investigated as a possible dosimeter for radiation therapy applications. Coumarin-3-carboxylic acid in aqueous solutions converts upon irradiation to the highly fluorescent 7-hydroxy-coumarin-3-carboxylic acid. The intensity of the fluorescence signal is linearly proportional to the number of the formed 7-hydroxy-coumarin-3-carboxylic acid molecules, which in turn is proportional to the radiation-absorbed dose. Basic characterization of the dosimetric properties (linearity with dose, energy and dose-rate dependence, postirradiation stability, and reproducibility) was performed. The system exhibits nearly linear behavior with dose, in the range of 0.1 to 50 Gy, is stable for at least 166 days following the irradiation, is reproducible within the same solution (+/- 2%) and is energy independent for 6- to 15-MV x-ray energies. A reduction of 18% of the fluorescence signal was observed by changing the dose rate from 0.8 to 4 Gy/min. The origin of the dose-rate effect was investigated and attributed to impurities, predominantly transition metal ions. Removing the impurities by recrystallization of the coumarin and using ultrahigh-purity water reduced the dose-rate dependency to less than 4% in the examined dose-rate range (0.8-4 Gy/min).

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma.

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.

Dynamic field shaping for stereotactic radiosurgery: a modeling study.

PURPOSE: This work assesses the relative field shaping advantages of dynamic field shaping devices for stereotactic radiosurgery using a linear accelerator. METHODS AND MATERIALS: We selected 43 intracranial tumors (2.0-4.2 cm maximum dimension, 1.5-25.5 cc tumor volume) out of the first 64 intracranial tumors treated with radiosurgery at the Joint Center for Radiation Therapy. We modeled five field shaping devices, each including a fixed auxiliary circular collimator: (a) fixed circular collimator alone; (b) two independent parallel jaws; (c) four independent rectangular jaws; (d) four independent rotatable jaws; and (e) "ideal" multileaf collimator. We adjusted the model parameters until the minimum target isodose was 80% of the dose delivered to isocenter. We defined the treatment volume ratio as the target volume divided by the treatment volume (volume receiving at least the minimum target dose). We used the treatment volume ratio to compare the five models and the actual patient treatments. RESULTS: For 34 tumors originally treated with one isocenter, the median Treatment Volume Ratio was higher for all of the device models except the fixed circular collimator compared to the actual patient treatments. For the nine tumors originally treated with multiple isocenters, the median Treatment Volume Ratio for the actual multiple isocenter treatments was similar to that for two parallel jaws, four rectangular jaws and four rotatable jaws. Only the median "ideal" collimator treatment volume ratio was higher for these nine tumors. CONCLUSION: Simple field shaping devices have approximately 50% of the conformal advantage of an "ideal" multileaf collimator. Approximately 50% of typical radiosurgical tumors between 2 and 4 cm have field shaping advantages which exceed the geometrical uncertainties inherent in linear accelerator radiosurgery treatments. The three models, two parallel, four rectangular, or four rotatable independent jaws would improve current linear accelerator technology by providing homogeneous doses with equivalent field shaping for most tumors originally treated with inhomogeneous multiple isocenter plans (6/9 tumors in the current series).

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma.

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

Quality assurance in stereotactic radiosurgery using a standard linear accelerator.

Methods have recently been developed for using standard linear accelerators to perform stereotactic radiosurgery. The accuracy necessary to perform this procedure requires an intensive quality assurance program to encompass all aspects of dose calibration and mechanical integrity of the treatment unit, the treatment planning process, and treatment delivery. The programs developed at the Joint Center for Radiation Therapy (JCRT) include testing of the linear accelerator and the stereotactic system, cross checking of the treatment planning process, and a quality assurance check list of the treatment delivery procedure. This report outlines in detail the quality assurance program currently in use at the JCRT.

An external beam treatment technique for retinoblastoma.

The main difficulty in the irradiation of retinoblastoma has been to deliver a high uniform dose to the entire retinal surface and spare the lens. Conventional techniques are inadequate to deliver an acceptable dose distribution especially for cases when there are both anterior and posterior lesions. We have developed a procedure to deliver a high dose anteriorly at the ora serrata for a compromise of about 30-35% of the target dose to the lens. The technique consists of 3 pairs of non-coplanar arcs using a 4 MV accelerator. This technique may offer a higher probability of tumor control and cure when gross tumor is present at the ora serrata when compared to the conventional techniques using lateral techniques.

Measurements of dose distributions in small beams of 6 MV x-rays.

Dose distributions produced by small circular beams of 6 MV x-rays have been measured using ionisation chambers of small active volume. Specific quantities measured include tissue maximum ratios (TMR), total scatter correction factors (St), collimator scatter correction factors (Sc) and off-axis ratios (OAR). Field sizes ranged from 12.5 to 30 mm diameter, and were defined by machined auxiliary collimators with the movable jaws set for a 4 cm x 4 cm field size. Due to the lack of complete lateral electronic equilibrium for these small fields, the accuracy of the measurements was also investigated. This was accomplished by studying dose response as a function of detector size. Uncertainties of 2.5% were observed for the central axis dose in the 12.5 mm field when measuring with an ionisation chamber with a diameter of 3.5 mm. The total scatter correction factor exhibits a strong field size dependence for fields below 20 mm diameter, while the collimator scatter correction factor is constant and is defined by the setting of the movable jaws. Off-axis ratio measurements show larger dose gradients at the beam edges than those achieved with conventional collimator systems. Corrected profiles measured with an ionisation chamber are compared with measurements made with photographic film and LiF thermoluminescent dosemeters.

Head scatter data for several linear accelerators (4-18 MV).

Measurements were made in air on the central axis of radiation beams from linear accelerators operating in the energy range from 4 to 18 MV, to determine the magnitude and source of head scattered radiation. Machines of several manufacturers were studied. The data indicate that, except for one unique collimator design, head scatter originates primarily in the flattening filter and is relatively independent of energy and machine.

A high-resolution digital dosimetric system for spatial characterization of radiation fields using a thermoluminescent CaF2:Dy crystal.

A high-resolution digital dosimetric system has been developed for the spatial characterization of radiation fields. The system comprises the following: 0.5-mm-thick, 25-mm-diam CaF2:Dy thermoluminescent crystal; intensified charge coupled device video camera; video cassette recorder; and a computerized image processing subsystem. The optically flat single crystal is used as a radiation imaging device and the subsequent thermally stimulated phosphorescence is viewed by the intensified camera for further processing and analysis. Parameters governing the performance characteristics of the system were measured. A spatial resolution limit of 31 +/- 2 microns (1 sigma) corresponding to 16 +/- 1 line pairs/mm measured at the 4% level of the modulation transfer function has been achieved. The full width at half maximum of the line spread function measured independently by the slit method or derived from the edge response function was found to be 69 +/- 4 microns (1 sigma). The high resolving power, speed of readout, good precision, wide dynamic range, and the large image storage capacity make the system suitable for the digital mapping of the relative distribution of absorbed doses for various small radiation fields and the edges of larger fields.

Progress in 3-D treatment planning for photon beam therapy.

The purpose of this report is to study the feasibility of improving dose distributions using non-coplanar photon beams from a linear accelerator. Non-coplanar beams may enter the patient in any arbitrary configuration. This type of treatment technique requires a three-dimensional (3-D) planning system. Clinical examples are used to illustrate the general problems in 3-D treatment planning, and the potential improvement over coplanar beam treatments. Features of a treatment planning system for 3-D planning are discussed.

A beam alignment device for matching fields.

When radiation treatment is delivered to adjacent or contiguous tumor volumes with multiple fields, the geometric alignment of the beams is particularly critical. A beam alignment device has been developed that enables precise matching of such fields.

Image quality of an analog radiation therapy simulator-based tomographic scanner.

The spatial resolution and noise level of images produced by a commercial analog tomographic scanner have been measured and compared to those of images reconstructed digitally from projections from the same detector. The full width at half maximum of the line spread function was 3.6 mm for images from the analog scanner and 1.1 mm for the digitally reconstructed images. The standard deviation of the CT numbers over a 10-cm2 circular area at the center of a large water phantom, calculated as a percentage of the linear attenuation coefficient of water, was 3.5% for the analog images, 15.4% for high-resolution digital images, and 3.2% for digital images reconstructed using a convolution filter which reduced the resolution to that of the analog images. The data contributing to each digital image were fewer than those contributing to each analog image by a factor of 10. The noise level did not depend on tube current in either the analog or the digital images. The utility of this analog device in radiation therapy planning will depend upon whether errors in contour localization resulting from transferring data from diagnostic CT scanners exceed the errors due to its poorer image quality.

Quality assurance in radiation therapy: physics efforts.

During the last two years, several important documents on quality assurance in radiation therapy have been published. In 1981 the Committee on Radiation Oncology Studies, in a report to the Director of the National Cancer Institute, outlined criteria for multidisciplinary cancer management, including technical standards in radiation therapy. In March 1983, a task group of the American Association of Physicists in Medicine (AAPM) submitted a document for review and publication on "The Physical Aspects of Quality Assurance in Radiation Therapy". This document addresses quality assurance problems related to: 1. treatment machines; 2. measurement equipment; 3. treatment planning; 4. treatment verification; 5. brachytherapy; and 6. radiation safety. One chapter in this latter document discusses the problem of estimating the uncertainty in dose delivered to a patient. The contributions to this uncertainty are analyzed and separated into dosimetric and spatial uncertainties. The dosimetric uncertainties resulting from the central axis calibration and treatment planning amount to about 5% at the 95% confidence level in an optimal situation. The spatial uncertainties resulting from machine alignment problems combined with patient set-up and organ motion may be about 8 mm to 10 mm, corresponding to two standard deviations. An example of how the spatial uncertainty translates into a dose uncertainty for a three-field esophageal plan is discussed.