Normal Brain Dose Research Articles

Dose distribution and clinical response of glioblastoma treated with boron neutron capture therapy

The dose distribution and failure pattern after treatment with the external beam boron neutron capture therapy (BNCT) protocol were retrospectively analyzed. BSH (5 g/body) and BPA (250 mg/kg) based BNCT was performed in eight patients with newly diagnosed glioblastoma. The gross tumor volume (GTV) and clinical target volume (CTV)-1 were defined as the residual gadolinium-enhancing volume. CTV-2 and CTV-3 were defined as GTV plus a margin of 2 and 3 cm, respectively. As additional photon irradiation, a total X-ray dose of 30 Gy was given to the T2 high intensity area on MRI. Five of the eight patients were alive at analysis for a mean follow-up time of 20.3 months. The post-operative median survival time of the eight patients was 27.9 months (95% CI=21.0–34.8). The minimum tumor dose of GTV, CTV-2, and CTV-3 averaged 29.8±9.9, 15.1±5.4, and 12.4±2.9 Gy, respectively. The minimum tumor non-boron dose of GTV, CTV-2, and CTV-3 averaged 2.0±0.5, 1.3±0.3, and 1.1±0.2 Gy, respectively. The maximum normal brain dose, skin dose, and average brain dose were 11.4±1.5, 9.6±1.4, and 3.1±0.4 Gy, respectively. The mean minimum dose at the failure site in cases of in-field recurrence (IR) and out-field recurrence (OR) was 26.3±16.7 and 14.9 GyEq, respectively. The calculated doses at the failure site were at least equal to the tumor control doses which were previously reported. We speculate that the failure pattern was related to an inadequate distribution of boron-10. Further improvement of the microdistribution of boron compounds is expected, and may improve the tumor control by BNCT.

Radiosurgery of functioning pituitary adenomas: Comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT

Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA). Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8–10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: D max optic chiasm 10Gy temporal lobe 10Gy temporal lobe. Results: For the end point "improvement in coverage," an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol 10Gy temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol 10 Gy temporal lobe was max optic chiasm Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA.

246 Oral Can we gain from complexity? Optimization of stereotactically-guided conformal radiotherapy of brain tumours based on normal brain dose volume histograms

246 Oral Can we gain from complexity? Optimization of stereotactically-guided conformal radiotherapy of brain tumours based on normal brain dose volume histograms

Optimization of stereotactically-guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms

Purpose: To investigate the optimal treatment plan for stereotactically-guided conformal radiotherapy (SCRT) of sellar and parasellar lesions, with respect to sparing normal brain tissue, in the context of routine treatment delivery, based on dose volume histogram analysis.Methods and Materials: Computed tomography (CT) data sets for 8 patients with sellar- and parasellar-based tumors (6 pituitary adenomas and 2 meningiomas) have been used in this study. Treatment plans were prepared for 3-coplanar and 3-, 4-, 6-, and 30-noncoplanar-field arrangements to obtain 95% isodose coverage of the planning target volume (PTV) for each plan. Conformal shaping was achieved by customized blocks generated with the beams eye view (BEV) facility. Dose volume histograms (DVH) were calculated for the normal brain (excluding the PTV), and comparisons made for normal tissue sparing for all treatment plans at ≥80%, ≥60%, and ≥40% of the prescribed dose.Results: The mean volume of normal brain receiving ≥80% and ≥60% of the prescribed dose decreased by 22.3% (range 14.8–35.1%, standard deviation σ = 7.5%) and 47.6% (range 25.8–69.1%, σ = 13.2%), respectively, with a 4-field noncoplanar technique when compared with a conventional 3-field coplanar technique. Adding 2 further fields, from 4-noncoplanar to 6-noncoplanar fields reduced the mean normal brain volume receiving ≥80% of the prescribed dose by a further 4.1% (range −6.5–11.8%, σ = 6.4%), and the volume receiving ≥60% by 3.3% (range −5.5–12.2%, σ = 5.4%), neither of which were statistically significant. Each case must be considered individually however, as a wide range is seen in the volume spared when increasing the number of fields from 4 to 6. Comparing the 4- and 6-field noncoplanar techniques to a 30-field conformal field approach (simulating a dynamic arc plan) revealed near-equivalent normal tissue sparing.Conclusion: Four to six widely spaced, fixed-conformal fields provide the optimum class solution for the treatment of sellar and parasellar lesions, both in terms of normal brain tissue sparing and providing a relatively straightforward patient setup. Increasing the number of fields did not result in further significant sparing, with no clear benefit from techniques approaching dynamic conformal radiotherapy in the cases examined.

A Quantitative Comparison of Fixed Conformal Beams vs. Arcs for Idealized Regular- and Irregular-Shaped Lesions

Fixed-shaped fields are compared to arcs for moderate-sized spherical- and ellipsoidal-shaped lesions, based on four measures: dose-volume histograms (DVHs), normal tissue complication probabilities (NTCPs), target dose heterogeneity (maximum dose in treatment volume in relation to prescription dose), and conformity index (prescription isodose volume in relation to target volume). To quantify lesion shape eccentricity distribution in a series of patients treated with conformal radiation. Dose calculations were performed with idealized irregular targets placed centrally and peripherally in the brain of a real patient data set. The three-dimensional (3-D) targets were defined as ellipsoids, characterized by two equal axes and one unequal axis (eccentricity is the ratio of unequal axis to equal axis). Target eccentricities were chosen based on an assessment of lesion eccentricity for a series of 30 consecutive patients treated with focused radiation. For centrally and peripherally located targets, dose calculations were performed with three, five, and seven fixed conformal beams (maximally distributed in feasible space), 480° collimated arcs (circular, elliptic, and continuously conformal collimation), and circularly collimated customized arcs (of total arc angle from 450°–1000°). For peripheral targets, coplanar and conical beam arrangements were also investigated. Wedges were used in all fixed beam cases to reduce target dose heterogeneity. The resulting DVHs, NTCPs, dose heterogeneity, and conformity indices for brain were compared for targets of variable eccentricity. In all beam arrangements tested, increasing the number of fixed conformal fields from three to five to seven decreases the normal brain volume at high dose and increases the normal brain volume at low dose, with diminishing differences as the number of fields increase. Among beam arrangements, seven fixed conformal beams maximally distributed in usable space (for peripheral or central targets) and seven fixed fields arranged in a cone (for peripheral targets) irradiated the least volume of normal tissue and had the lowest NTCPs. Within the class of beam arrangements that had the lowest normal brain volumes and NTCPS, fixed conformal beams maximally separated in space, dose heterogeneity, and conformity index remained relatively constant in going from three to five to seven beams. Among arc arrangements, in general, the 480° continuously conformal arc had the least normal tissue irradiation at high and low doses, and lowest NTCPs. Dose heterogeneity was relatively constant with increasingly tighter collimation among the 480° arc arrangements, i.e., circular to elliptic to conformal, while the conformity index improved significantly. Further improvements in DVH, NTCP, conformity index, and dose heterogeneity were provided by certain customized arc arrangements. In general, for all eccentricities and target locations, seven fixed fields maximally distributed in space were similar to the 480° continuously conformal arc in respect to normal brain volumes, NTCPs, dose heterogeneity, and conformity index. For both peripheral and central targets of variable eccentricity, the 480° continuously conformal arcs and seven fixed conformal fields (maximally separated in feasible space for central and peripheral lesions/arranged in a cone for peripheral lesions) appear to be very similar in respect to normal brain volumes, NTCPs, dose heterogeneity, and conformity index. They are overall superior to the other options tested.

A comparison of three stereotactic radiotherapy techniques; ARCS vs. noncoplanar fixed fields vs. intensity modulation

Purpose: Linac arc based stereotactic radiotherapy is being used with increasing frequency to treat brain tumors. This approach can be used for single or fractionated treatments, and is typically carried out with circular collimators which are optimal for small, spherical targets. Treatment planning using fixed noncoplanar beams or intensity-modulated beams may enhance the ability to conform to irregularly shaped and/or large tumors, especially when combined with stereotactic localization. We compare the dose conformity and normal brain dose characteristics of three stereotactic techniques for various nonspherical target shapes.Methods and Materials: Three intracranial test targets were constructed using a 3D treatment planning system after a patient underwent CT simulation. The targets included an ellipsoid with major axis dimensions of 4.0, 2.0, and 2.0 cm, a hemisphere with a diameter of 4.0 cm, and an irregularly shaped patient tumor with a maximum dimension of 5.3 cm. The following stereotactic techniques were compared for each target: a) 5 arcs as used in traditional linac radiosurgery/radiotherapy (noncoplanar arcs [ARCS]), b) 6 fixed noncoplanar custom blocked fields (3D), c) intensity modulation using 6 noncoplanar beams and a mini-multileaf collimator (intensity-modulated radiation therapy [IMRT]). Dose volume histograms were performed for each target/technique combination.Results: For the ellipsoid, dose conformity is similar for all three techniques and normal brain isodose distributions are more favorable with the ARCS plan. For the hemisphere and irregular tumor targets, dose conformity and high/low isodose normal brain volumes are more favorable with the IMRT technique.Conclusions: For the targets described above, the intensity-modulated technique results in improved dose conformity and decreased dose to nontarget brain in high and low isodose regions as compared to the standard noncoplanar arc technique or noncoplanar fixed fields for the hemisphere and tumor targets. Intensity-modulated treatment delivery may allow for an increase in the therapeutic ratio for treating stereotactically defined large and/or irregularly shaped intracranial targets.

Monte Carlo-based treatment planning for boron neutron capture therapy using custom designed models automatically generated from CT data

Purpose : A Monte Carlo-based treatment planning code for boron neutron capture therapy (BNCT), called NCTPLAN, has been developed in support of the NeW England Medical Center-Massachusetts Institute of Technology program in BNCT. This code has been used to plan BNCT irradiations in an ongoing peripheral melanoma BNCT protocol. The concept and design of the code is described and illustrative applications are presented. Methods and Materials : NCTPLAN uses thin-slice Computed Tomography (CT) image data to automatically create a heterogeneous multimaterial mathematical model of the relevant body part, which is then used as input as isocontours superimposed on precisely corresponding CT images of the body part. Currently the computational slowness of the dose calculations precludes efficient treatment planning per se, but does provide the radiation oncologist with a preview of the doses that will be delivered to tumors and to various normal tissues, and permits neutron irradiation times in Megawatt-minutes (MW-min) to be calculated for specific dose prescriptions. The validation of the NCTPLAN results by experimental mixed-field dosimetry is presented. A typical application involving a cranial parallel-opposed epithermal neutron beam irradiation of a human subject with a glioblastoma multiforme is illustrated showing relative biological effectiveness-isodose (RBE) distributions in normal CNS structures and in brain tumors. Parametric curves for the MITR-II M67 epithermal neutron beam, showing the gain facotrs (gain factor = minimum tumor dose/maximum normal brain (dose) for a various combinations of boron concentrations in tumor and in normal brain, are presented. Results : The NCTPLAN code provides good computational agreement with experimental measurements for all dose components alon the neutron beam central axis in a head phantom. For the M67 epithermal beam the gain factor for 1, boronophenylalanine for a small midline brain tumor under typical distribution assumptions is 1.4−1.8×. Implementation of the code under clinical conditions is demonstrated. Conclusion : The NCTPLAN code has been shown to be well suited to treatment-planning applications in BNCT. Comparison of computationally derived dose distributions in a phantom compared with experimental measurements demonstrates good agreement. Automatic superposition of isodose contours with corresponding CT image data provides the ability to evaluate BNCT doses to tumor and to normal structures. Calculation of gain factors suggests that for the M67 epithermal neutron beam, more advantage is gained for increasing boron concentrations in tumor than from increasing the boron tumor-to-normal brain ratio.