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A five-field conformal technique with three-dimensional radiation therapy treatment planning (3-DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five-field conformal 3-DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty-two consecutive patients with nonsmall-cell lung carcinoma (NSCLC) were evaluated during the years 1993–1997. The median age was 60 years (range 34–80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000–6,840 cGy) delivered over 6 to 6.5 weeks in 180–275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2-week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3–773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow-up was 11.2 months (range 3–32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3 ± 11.4% at 2 years. However, for Stage III patients, local control was 50% at 1 year and 30% at 2 years. Patients who received concurrent chemotherapy had significantly improved survival (P = 0.002) and local control (P = 0.004), compared with RT alone. Late esophageal toxicity of ≥Grade 3 occurred in 14.1 ± 9.3% of patients (3 of 20) receiving combined chemoradiotherapy, but in none of the 15 patients treated with RT alone. Pulmonary toxicity limited to Grades 1–2 occurred in 6.8% of the patients, and none developed ≥Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, present a challenge for adequate dose delivery without significant toxicity. Our five-field conformal 3-DRTP technique, which incorporates treatment planning by dose/volume histogram (DVH) was associated with minimal toxicity and may facilitate dose escalation to the gross tumor. Radiat. Oncol. Invest. 7:297–308, 1999. © 1999 Wiley-Liss, Inc.

A measurable improvement in the efficacy of the three-dimensional radiotherapy (RT) of primary lung cancer patients with unresectable disease will require the development of a technique that increases the therapeutic ratio of dose delivered to the tumor volume relative to functional lung. A full course of definitive RT dose was delivered to six consecutive primary lung cancer patients using multiple fields with treatment portals tightly conformed to the tumor shape in beams-eye-view, using multileaf collimation. For each patient, a treatment planning dose/volume histogram (DVH) was constructed considering the most anatomically normal tissues in both the ipsilateral and contralateral lungs. When compared to a standard anteroposterior-posteroanterior (AP-PA) treatment plan followed by parallel-opposed oblique fields with conventional blocks, the five-field conformal technique yielded a significantly lower integral lung dose as determined by cumulative DVH data. We compared the data for total lung capacity in cubic centimeters from the treatment planning DVH with that obtained by pulmonary function tests and found good concordance. The present RT technique and patient evaluation program should provide a valuable approach toward improving the quality of life in irradiated lung cancer patients, and may also guide efforts by which to escalate the dose to a tumor volume in the chest. © 1995 Wiley-Liss, Inc.

The aim of the study was to analyze whether the fixation of the stereotactic frame is stable and whether the location of the treated target coincides with its anatomical location during Gamma Knife® surgery (GKS). Stereotactic MR examinations using the same high-resolution MRI protocol were performed before and after GKS in 18 consecutive patients. The stereotactic (x,y,z) coordinates for three different anatomical landmarks were independently defined three times in each study for each landmark of the images taken before and after GKS by two of the authors, resulting in a total of 648 coordinate definitions. The uncertainty in the readings of the coordinates for the anatomical landmarks was of the same magnitude as the difference in the coordinates before and after GKS in all but one patient. The differences in this one case were due to MR distortion and not to repositioning of the frame. The difference in the coordinates before and after treatment was not affected by the removal of one of the frontal fixation screws in one of the patients. The stereotactic frame position is stable and does not move.

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Metal Oxide-Silicon Field Effect Transistor or MOSFET radiation detectors have become excellent in-vivo dosimeters for radiation therapy, but the MOSFET dosimeter's responses to clinical electron beams have yet to be fully evaluated. The authors measured MOSFET dose responses to varying electron beam energies and angles on patients and anthropomorphic phantoms. MOSFET responses in mV per cGy are compared against electron skin doses determined using a thin parallel plate ionization chamber. Results indicate the MOSFET dosimeter is near energy independent to within 1%. The MOSFET responses are dependent on the electron source to patient skin distances (SSD) within +/-5%, indicative of some dependence on dose rate or accelerator pulse rate by the field effect transistor. These SSD responses compare favorably with the response typically observed with diode in vivo dosimeters, except at extremely short SSD (i.e., 95 cm) close to the mouth of the electron cones where both the chamber and the MOSFET or diode readings are difficult to interpret. MOSFET responses correlated within 2% of the doses in different electron field sizes including blocked or small cutout down to 4 cm. The authors concluded MOSFET is dosimeter suitable in electron beams and it necessitates only a nominal dose calibration factor for in-vivo dosimetry treatment field conditions, except when patient treatment distances are considerably greater (20 cm) than accelerator nominal isocenter.

Objective Clinical studies have demonstrated a significant association between the presence of extensive postlumbar discectomy peridural scar formation and the recurrence of low back and radicular pain. Low-dose perioperative radiation therapy has previously been demonstrated to inhibit peridural fibrosis after laminectomy in a rat model. The current study was designed to measure the effect of low-dose radiation on postlaminectomy peridural fibrosis development in a larger animal model. Methods Three dogs underwent a total of 12 lumbar hemilaminectomies. For each animal, two levels received 1) external beam radiation 24 hours before surgery, 2) surgery alone, or 3) radiation alone. Radiation was administered in a single fraction of 700 cGy using computed tomographic guidance for dosimetry planning. The isodose distribution was such that the dose conformed to the posterior epidural space with minimal exit dose to normal tissue. Port films were used to confirm the correct levels. Gadolinium-enhanced magnetic resonance imaging (MRI) of the lumbar spines was obtained before the animals were killed 12 weeks after surgery. The spines were harvested, and axial sections through the laminectomy defect were stained with hematoxylin and eosin and Masson's trichrome. All specimens were evaluated for extent of fibrosis along the dura, density of fibrosis, nerve root entrapment, and sublaminar fibrosis. Results There were no complications from the surgery, and no new neurological deficits were noted. There was a statistically significant difference between the irradiated and nonirradiated groups regarding the extent of fibrosis (P = 0.001) and the density of fibroblasts (P = 0.001). There was also a marked difference in nerve root entrapment (P = 0.182) and the presence of sublaminar fibrosis (P = 0.061) between the treatment and control groups. MRI revealed less gadolinium enhancement at the irradiated levels compared with the nonirradiated levels, confirming the usefulness of MRI in predicting the degree of epidural fibrosis. Conclusion Low-dose external beam radiation therapy administered 24 hours before laminectomy in a dog model significantly decreased the extent and density of peridural fibrosis as well as nerve root entrapment and sublaminar fibrosis. This treatment strategy may be efficacious in patients with recurrent radicular pain after lumbar discectomy that is thought to be secondary to peridural fibrosis on the basis of gadolinium-enhanced MRI studies, and who might benefit from reoperation for nerve root decompression.

Purpose : Microdosimetric expectations of Boron contents are extracted from a CRAY-Monte Carlo stimulation of the nuclear reaction 10B(n, α)7Li as it occurs on a boronated membrane of a model cell and as the reaction fragments (α and Li) traverse into the cellular nucleus. Methods and Materials : The present microdosimetry calculation is based upon the assumption that the therapeutic advantage of boron neutron capture therapy (BNCT), while depending upon the RBE and LET of the reaction particles, is equally dependent on the boron carrier preferential localization to tumor tissue, and the boron selectivity to cancerous cells and its specificity within the subcellular compartments. In particular, boron fixes to cell membrane as it ought to, using monoclonal antibodies. The present Monte Carlo simulation computes stochastic expectations of α/Li energy depositions to the nucleus in a uniformly boronated membrane shell of a spherical cell. Differential energy gain was deduced from the stochastic energy depositions in events of neutron reactions with membrane boron compared against those with natural elements (O, H, N) in the cell. Results : Microdosimetry data are presented in terms of specific energy ( z keV μ 3 ) and lineal energy (keV/μ) functions of the nucleus-to-cell volume rations (NCVR). When folded with the geometric boron content and accounting for background reaction energies, the distributions yield effective energy gain to the cell nucleus per neutron capture event. Boron amount required to yield these energy gains found to be of the order of picograms of boron per gram of cell mass. Conclusions : The boron content as inferred by the present Monte Carlo microdosimetry compares well with that deliverable by present pharmacokinetic means, but are orders of magnitude (μ-grams) less than those deduced previously from anthropomorphic macrodosimetry.

Mathematical models were developed to predict tolerance of brain tissue to stereotactic radiosurgery. The use of these formulas for predicting symptomatic brain necrosis from stereotactic radiosurgery with the 60Co gamma unit is discussed. Predicted dose-response curves for different collimator sizes were calculated. Dose-volume isoeffect curves for a 3% risk of brain necrosis from a single fraction radiosurgery were then derived. Dose-volume isoeffect curves for combinations of fractionated whole brain irradiation with radiosurgery boosts were also calculated. The predicted dose-volume isoeffect curves provide useful tolerance guidelines for the practice of stereotactic radiosurgery.

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented.

An exact formula used for determination of the magnification of the target using the conventional stereotactic biplane radiographic imaging has been derived for the stereotactic frame.

Polyacrylamide-based tissue-equivalent phantoms simulating cortical bone and muscle are described. The equivalency is based upon similar elemental composition and density, and partial similarity in the morphology of bone. Satisfactory results were obtained when the phantoms were tested at low (20 keV) and high (15 MeV) gamma radiation. Applicability of this phantom material to neutron transport is discussed. The material can be molded and shaped and its composition is easily modified by altering the proportions of the constituents. Trace elements or radionuclides are easily added. Details of the physical and radiation characteristics of the formulated systems are given together with the manufacturing procedures.

The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.