Shrikant S. Kubsad

Defining the role of radiosurgery in the management of brain metastases

The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.

Stereotactic radiosurgery for glioblastoma multiforme: Report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage

PURPOSE Prospective evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma. METHODS AND MATERIALS From 5/89 to 12/92, 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery, in addition to 54 Gy in 1.8 Gy/fraction following biopsy (n = 12) or resection (n = 19). Eligibility required supratentorial glioblastoma, tumor not > 4 cm in > 1 axis, age > 18 years, and location > 1 cm from optic chiasm. Patient characteristics were: age 20-78 years (median = 57); 22 male, 9 female; Karnofsky score 20-90 (m = 70), and volume of 2.3-59.7 c.c. (m = 17.4). Eighteen patients were treated with 1 collimator, 5 with 2, 7 with 3, and 1 with 4; peripheral isodoses were 40-90% (m = 72.5) and minimum and maximum tumor dose ranges were 10-20 (m = 12) and 15-35 Gy (m = 18.75). Patients were followed clinically and radiographically every 8-12 weeks to analyze survival, quality of life, and toxicity. RESULTS With a follow-up of 12-171 weeks, 8 out of 31 (26%) patients are alive. Median survival is 42 weeks. Twelve and 24-month actuarial survival are 38 and 28%. Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7% (p < 0.05). Extent of resection and performance status were associated with improved survival in a multivariate analysis. No significant acute toxicity was encountered. Four patients (13%) developed clinically significant necrosis verified by biopsy or positron emission tomography scan at 9-59 weeks after radiosurgery. CONCLUSION The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine, but the 2-year survival may be superior. Future randomized trials of radiosurgery are recommended, and ad hoc use of this modality should be discouraged.

Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database

Twenty-one arteriovenous malformations were prospectively evaluated using magnetic resonance angiography and compared with stereotactic angiography. The goals were to establish the feasibility of magnetic resonance angiography, compare it to stereotactic angiography, employ magnetic resonance angiography in follow-up, and semiquantify flow. A correlative evaluation between flow and response to stereotactic radiosurgery was carried out. Phase contrast angiograms were obtained at flow velocities of 400, 200, 100, 60, and 20 cm/sec. The fractionated velocities provided images that selectively demonstrated the arterial and venous components of the arteriovenous malformations. Qualitative assessment of the velocity within the arteriovenous malformations and the presence of fistulae were also determined by multiple velocity images. In addition, 3-dimensional time-of-flight magnetic resonance angiograms were obtained to define the exact size and shape of the nidus. This technique also permitted evaluation of the nidus and feeding arteries for the presence of low flow aneurysms. Correlation between the two imaging modalities was carried out by subjective and semiquantitative estimation of flow velocity and estimation of nidus size. The following velocity parameters were employed: fast, intermediate, slow, and none (arteriovenous malformation obliterated). In 19 of 21 (90.5%) arteriovenous malformations, magnetic resonance angiography was equal or superior to stereotactic angiography for flow quantification and visualization of the nidus. Only 2 of 21 arteriovenous malformations were better demonstrated by stereotactic angiography than by magnetic resonance angiography (failure rate of 9.5%). The nidus size in one case was clearly underestimated by stereotactic angiography and would have resulted in a geographic miss without magnetic resonance angiography. Seven post-radiosurgery arteriovenous malformations were evaluated for follow-up with both magnetic resonance angiography and stereotactic angiography. In 6 of 7 arteriovenous malformations, magnetic resonance angiography response matched stereotactic angiography response. Correlation of flow with outcome was carried out for 14 arteriovenous malformations using magnetic resonance angiography only. Interestingly, all nine arteriovenous malformations with intermediate or slow flow demonstrated partial or complete obliteration; whereas only 3 of 5 fast flow arteriovenous malformations achieved a response with a median follow-up of 10 months. This early analysis suggests that slower flowing arteriovenous malformations may obliterate faster after stereotactic radiosurgery and flow parameters could be employed to predict response. In conclusion, magnetic resonance angiography permits semiquantitative flow velocity assessment and may therefore be superior to stereotactic angiography. An additional advantage of magnetic resonance angiography is the generation of serial transverse images which can replace the conventional CT scan employed for stereotactic radiosurgery treatment planning.(ABSTRACT TRUNCATED AT 400 WORDS)

Monte Carlo and convolution dosimetry for stereotactic radiosurgery

The dosimetry of small photon beams used for stereotactic radiosurgery was investigated using Monte Carlo simulation, convolution calculations, and measurements. A Monte Carlo code was used to simulate radiation transport through a linear accelerator to produce and score energy spectrum and angular distribution of 6 MV bremsstrahlung photons exiting from the accelerator treatment head. These photons were then transported through a stereotactic collimator system and into a water phantom placed at isocenter. The energy spectrum was also used as input for the convolution method of photon dose calculation. Monte Carlo and convolution results were compared with the measured data obtained using an ionization chamber, a diode, and film.

A three-dimensional volume visualization package applied to stereotactic radiosurgery treatment planning☆

A comprehensive software package has been developed for visualization and analysis of 3-dimensional data sets. The system offers a variety of 2- and 3-dimensional display facilities including highly realistic volume rendered images generated directly from the data set. The package has been specifically modified and successfully used for stereotactic radiosurgery treatment planning. The stereotactic coordinate transformation is determined by finding the localization frame automatically in the CT volume. Treatment arcs are specified interactively and displayed as paths on 3-dimensional anatomical surfaces. The resulting dose distribution is displayed using traditional 2-dimensional displays or as an isodose surface composited with underlying anatomy and the target volume. Dose volume histogram analysis is an integral part of the system. This paper gives an overview of volume rendering methods and describes the application of these tools to stereotactic radiosurgery treatment planning.

Dosimetry of large wedged high‐energy photon beams

The dependence of the wedge factor and central axis depth dose on field size was evaluated for 6-, 10-, and 24-MV wedged photon beams for field sizes up to 40 x 40 cm2. The wedge factor for 60 degrees, 45 degrees, 30 degrees, and 15 degrees wedges in a 24-MV beam was found to vary by as much as 25%, 12%, 9%, and 5%, respectively, over a field size range of 5 x 5 to 40 x 40 cm2. For 10 and 6 MV wedged beams, the wedge factors varied by up to 17% and 15%, respectively, over the same field size range. The depth dose curves for the wedged beams differed significantly from the open beam profiles. At 6 MV, the wedges caused beam hardening while at 24 MV, with the exception of the 15 degrees wedge, all wedged beams were softer than the open beams, for all field sizes. At 10 MV, wedged fields of size less than 20 x 20 cm2 were hardened relative to the open beam, whereas larger wedged fields had depth dose values within +/- 1% of the 10-MV open-beam depth dose data. Accurate treatment planning for large wedged fields and high-energy photon beams thus requires the use of wedged beam depth dose curves and field size specific wedge factors. It was established that an equivalent square field for a rectangular wedged field can be determined using the standard open beam formulation. The largest difference between the wedge factor for a rectangular beam and its equivalent square beam was 2.5% and occurred for 24-MV elongated fields.(ABSTRACT TRUNCATED AT 250 WORDS)

On the cause of the variation in tissue‐maximum ratio values with source‐to‐detector distance

While tissue-maximum ratios (TMR) for 60cobalt treatment units have been shown to be independent of source-to-axis distance (SAD), high-energy photon beams demonstrate variations in their TMR as a function of SAD. Some authors have asserted that the distance dependence of the TMR stems from electron contamination in the beams, while others have suggested low-energy, scattered photons as the cause. Using a magnet to sweep contaminant electrons out of the photon treatment beam eliminates any variation in TMR with distance. Thus, electron contamination accounts for all of the distance dependence, and any low-energy, scattered photons behave indistinguishably like the high-energy photons.

90Y · B72.3 Against pancreatic cancer: Dosimetric and biological analysis

Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.

Weight Consideration in the Use of Cerrobend Beam Blocks

The technique of using customized field blocking to protect sensitive normal tissue during megavoltage radiation treatment is common practice in modern radiation therapy. The introduction of CT-based treatment planning has revolutionized customized field shaping. We carried out a prospective evaluation of 54 cerrobend blocks during a one-month time period. The goals of this study were to analyze the specific block patterns and correlate these with field size, block weight, and field setup. Factors contributing to excessively large and heavy cerrobend blocks defined as > or = 20 lbs. were identified. Twenty-two percent of blocks were found to be excessively large and one-third of these were a consequence of planning decisions. A review of these situations suggests that alternative methods would have avoided the excessive weight. Concerns have been raised regarding the safety of large and heavy cerrobend blocks. These blocks were therefore analyzed in terms of tray sag and tray break-point. Our data suggest that within this clinical range of block weight, neither tray sag nor tray break-point are of significant concern.