A.M. Kalend

Treatment planning for gamma knife radiosurgery with multiple isocenters

Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. Forty-eight percent of the first 156 patients treated with the gamma unit at the University of Pittsburgh required treatment with two or more isocenters to optimize dose distributions. Dose distributions for combining gamma knife treatments to two or more isocenters were systematically investigated. High speed computerized dosimetry was performed using specially developed software and dose distributions were confirmed with film densitometry. We have developed guidelines for treatment to two or more isocenters which help reduce treatment planning time, and facilitate selection of treatment doses and optimum dose distributions. These guidelines include maintaining an account of the distances between all isocenters, using a catalogue of sample two-isocenter isodose plans, comparing dose volume histograms, and calculating complication probabilities using the integrated logistic formula.

Treatment volume shaping with selective beam blocking using the leksell gamma unit

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.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

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.

Predicted Dose-Volume Isoeffect Curves for Stereotactic Radiosurgery with the 60Co Gamma Unit

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.

Clinical use of a wing field with transmission block for the treatment of the pelvis including the inguinal node

Treatment planning of photon and electron beams to include the pelvis and the groin poses a technical difficulty of positioning beams, and a dosimetric problem of abutting fields at the groin. We have analyzed a simpler AP/PA method using a central transmission block. The posterior portal is smaller and opposes only the pelvic portion of the anterior portal under the transmission block, while the anterior extended portion (hence the wing) is unattenuated to treat the inguinal region. By calculating the attenuation thickness according to the patients separation and the beam quality, the dose distribution is tailored to yield the proper dose to the pelvic mid-plane and the inguinal nodes while minimizing the dose to the femora. Measured dose distribution (6MV) using film dosimetry in a tissue-equivalent phantom indicates that a 30% hot spot is created by the posterior portal diverging into the wings of the anterior field. Therefore, the pelvic attenuator is tapered at its lateral edges, thereby significantly reduced the dose inhomogeneity (5%) at the groin. Clinical methods are outlined for the verification of the patient portal films against possible mismatch in beam divergence.

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams.

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 > or =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 > or =Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, presenta 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.

Transmission block technique for the treatment of the pelvis and perineum including the inguinal lymph nodes: dosimetric considerations.

Radical radiotherapy of pelvic malignancies (e.g., vulva, anus) includes therapeutic dosage to the inguinal nodes. To minimize the dosage to the femoral head, the transmission block technique has been developed to fully irradiate the central pelvis midplane and inguinal nodes. Originally, this technique compensated for dose inhomogeneity in the transverse plane only. In some patients, however, we have observed a significant dose variation along the sagittal plane. The authors have developed a lead compensation technique to homogenize the sagittal dose variations due to the longitudinal sloping in the patient, along with further refinements in this technique. Dosimetric and technical details are also discussed.

Comment on the recent results of Hopewell, Morris and Dixon-Brown on radiation myelitis produced by irradiation of very short segments of rat spinal cord

Recently, we proposed a model for radiation damage to normal tissue (Yaes & Kalend, 1988), based on the assumption that, because of the limited mobility and reproductive capacity of stem cells (Hellmann & Botnick, 1977) in adult mammalian organs, for each organ there is a maximum volume, which we have called the “critical volume”, that can be repopulated and repaired by a single surviving stem cell. When a critical volume is totally depleted of stem cells, irreparable damage results; however, a single surviving stem cell within the critical volume prevents the damage from occurring. These assumptions constitute the “local stem cell depletion hypothesis” (Yaes & Kalend, 1988). For the spinal cord, we represent the critical volume as a transverse “slice” of thickness t, assumed to be small compared with lengths of spinal cord usually irradiated clinically. If irreparable damage occurs to a single slice, the long motor and sensory tracts passing through it would be damaged, giving rise to radiation myelitis.

Point dose variations with time during traditional brachytherapy for cervical carcinoma

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

Dosimetric consequences of 10B(n,α)7Li reaction occurring at the cellular membrane

Abstract Purpose: Microdosimetric expectations of Boron contents are extracted from a CRAY-Monte Carlo stimulation of the nuclear reaction 10 B( n , α ) 7 Li 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 (zkeVμ3) 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.