IMRT or 3D-CRT in glioblastoma? A dosimetric criterion for patient selection.

Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.

SU-E-J-168: 4D-PET for Target Volume Delineation in Respiratory-Gated Radiation Therapy.

PURPOSE: To find an optimized workflow for the use of respiratory-gated PET (4D-PET) in target volume delineation of tumors subject to respiratory-gated radiation therapy. METHODS: 15 patients with lung (11) and pancreas (4) tumors who had FDG-PET-CT for target delineation prior to EBRT were studied. Patients were selected among the group that showed respiratory-induced tumor motion 〉5mm. 4D-PET was performed by means of a Philips Gemini BigBore scanner, using the Varian RPM gating system. An identical system was available at the linac for treatment. The breathing cycle was equally divided in 4 phases, according to a previous study. Since planning was made on a single CT-phase, no ITV was explicitly built from the set of phases. The BTV was identified with SUV=2.2 threshold and the PTV was obtained expanding the BTV by 8mm(S-I), 5mm(A-P) and 3mm(L-R) to account for residual motion and setup errors. The most advantageous CT-phase for treatment planning was then identified by simulating plans on each phase and analyzing the resulting DVHs of OARs (lung, trachea, oesophagus, spinal cord, left ventricle). RESULTS: The observed maximum range of motion was 5.5mm(L-R), 12.3mm(A-P) and 19.2mm(S-I). The standard deviation of the BTV volume in the 4 phases ranged from 6% to 13.7%. V20 (lung) ranged 7.1%-15.2% in inspiration and 7.8%-18.6% in expiration. The mean dose to the oesophagus ranged 0.1-2.2Gy in inspiration and 1.4-2.0Gy in expiration. In general, the dose to OARs was smaller when planning on a single phase than on the overall, respiratory-uncontrolled volume (p-value〈0.05). CONCLUSIONS: The BTV volume was almost constant between phases, confirming that the motion might be described by 4 phases. There was no obvious choice of the optimal phase for treatment planning, suggesting patient-by-patient studies. However, planning and delivery on one phase consistently allowed dose sparing to be obtained compared to non-gated techniques.

Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI.

OBJECTIVES: Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T(1) and T(2) weighted MRI was compared. METHODS: 4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T(1) contrast-enhanced (T1(PRE)CTV and T1(POST)CTV) and T(2) weighted images (T2(PRE)CTV and T2(POST)CTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes. RESULTS: The volumes of T1(PRE)CTV and T1(POST)CTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences >100 cm(3) were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T(2) volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1(PRE)CTV and T1(POST)CTV (CI = 0.67 ± 0.09), T2(PRE)CTV and T2(POST)CTV (CI = 0.39 ± 0.20) and comparing the portion of the T1(PRE)CTV and T1(POST)CTV not covered by that defined on T2(PRE)CTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively). CONCLUSION: Using T(2) MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T(1) MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T(1) weighted MRI for planning purposes.

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study.

PURPOSE: Hyperthermia has been used in several trials to treat pelvic cancers without excessive toxicity and with positive results. The aim of this study was to evaluate feasibility and results in terms of biochemical recurrence-free, disease-free survival, overall survival, and treatment toxicity profile of hyperthermia combined with radiotherapy in locally advanced high risk prostate cancer. PATIENTS AND METHODS: From November 1998 to December 2004, 144 patients with locally advanced prostate cancer (LAPC) were enrolled in a phase II study. They were treated using conformal radiotherapy (CRT) plus local hyperthermia (LHT) and androgen suppression therapy (AST). Treatment modalities consisted of: 1) CRT with a mean dose of 74 Gy (2 Gy/fraction/5 fractions per week); 2) LHT: one session per week during the first, second, third, and fourth week of the radiotherapy course; 3) AST was administered as neo-adjuvant and adjuvant therapy in more than 60% of patients. RESULTS: The median follow-up time was 51.7 months. Four patients were lost at follow-up. Of 140 evaluated patients, four died because of intercurrent diseases and 12 because of progression of disease. Patients were evaluated in terms of five-year overall survival (87%), and five-year biochemical progression-free survival (49%). No significant side effects, except symptoms related to AST have been reported. No late grade 3 toxicity occurred. CONCLUSIONS: In advanced high risk prostatic cancer, hyperthermia is feasible and well tolerated. It may be useful to enhance the radiotherapy efficacy at intermediate dose in order to avoid higher doses of irradiation which increases acute and late sequelae. The advantage of LHT combined with CRT should be confirmed by a randomized phase III trial, comparing irradiation plus AST with or without hyperthermia.

A method for the quantitative evaluation of SAR distribution in deep regional hyperthermia.

The Specific Absorption Rate (SAR) distribution pattern visualization by a matrix of E-field light-emitting sensors has demonstrated to be a useful tool to evaluate the characteristics of the applicators used in deep regional hyperthermia and to perform a quality assurance programme. A method to quantify the SAR from photographs of the sensor array--the so-called 'Power Stepping Technique'--has already been proposed. This paper presents a new approach to the quantitative determination of the SAR profiles in a liquid phantom exposed to electromagnetic fields from the Sigma-60 applicator (BSD-2000 system for deep regional hyperthermia). The method is based on the construction of a 'calibration curve' modelling the light-output of an E-field sensor as a function of the supplied voltage and on the use of a reference light source to 'normalize' the light-output readings from the photos of the sensor array, in order to minimize the errors introduced by the non-uniformity of the photographic process. Once the calibration curve is obtained, it is possible, with only one photo, to obtain the quantitative SAR distribution in the operating conditions. For this reason, this method is suitable for equipment characterization and also for the control of the repeatability of power deposition in time.

A euristic approach to the volume reconstruction of arteriovenous malformations from biplane angiography.

Three-dimensional (3D) volume reconstruction is easily feasible with axial, coronal or sagittal CT and MRI scans. On the other hand, radiosurgical treatment of arteriovenous malformations (AVMs) is exclusively based on two orthogonal stereotactic projections, obtained with angiographic procedures. Most commonly AVM volumes have been calculated by assimilating the nidus volume to a prolate ellipsoid. We present an algorithm dedicated to 3D volume reconstruction starting from two stereotactic orthogonal projections. This has been achieved using a euristic approach which has been widely adopted in the artificial intelligence domain. Tests on phantoms of different complexity have shown excellent results. The importance of the algorithm is considerable. Firstly, it allows calculations of complex structures far removed from a regular ellipsoid. Secondly, it permits shape recovery. Thirdly, it provides AVM visualization on axial planes.

Quality assessment of magnetic resonance stereotactic localization for Gamma Knife radiosurgery.

Artifacts in magnetic resonance imaging (MRI) may lead to anatomical distortion and inaccurate stereotactic coordinates. A special phantom for MRI and computed tomography (CT) was built to test the quality and precision of the two neuroradiological procedures. The phantom is fixed with the Leksell frame, and it has 15 orthogonal markers visible by CT and MRI techniques. The coordinates of the markers were calculated first on the CT scans and then on MR images. Two groups of different distortions were analysed: artifacts depending on the frame and its components and artifacts depending on the MR unit and image characteristics. A good target-coordinate correlation was found between CT and MRI in the axial plane, while in the coronal plane there was always a small error. This error is not constant, but changes from test to test, consequently it is hard to reform the image.

Gamma Knife radiosurgery in AIDS-related primary central nervous system lymphoma.

The frequency of AIDS-associated primary central nervous system (PCNS) lymphoma is rapidly increasing in adults and children. In AIDS-related PCNS lymphoma, different authors have reported an overall poorer response rate to conventional radiation compared with immunocompetent patients. This poorer response consists of a significantly positive, although transient effect on survival following radiotherapy (XRT), with a poor toleration for prolonged whole-brain RT (WBR) and with radiation-induced changes within the normal CNS tissue on autopsy examinations after a course of XRT. These observations led us to consider highly focused single-session radiosurgical treatments as a potentially useful therapeutic modality for AIDS-associated PCNS lymphomas. A multi-institutional diagnostic and therapeutic protocol for the evaluation and treatment of AIDS patients with high-risk intracerebral space-occupying lesions has been developed at the University Hospital of Verona. Therapy is based on tumor biopsy. Tumors < or = 3.5 cm in diameter are subjected to Gamma Knife radiosurgery, whereas tumors < or = 4.5 cm are treated with stereotactic brachytherapy. At the Department of Neurosurgery, Verona, Italy, Gamma Knife treatment was performed in 2 cases of deep-seated histologically verified malignant non-Hodgkin's lymphoma. A short-term cliniconeuroradiological follow-up (2 months later) showed neurologic improvement and virtually complete disappearance of the tumor in both patients. The excellent local control and the well-tolerated single-session treatment and absence of brain toxicity signs on CT scan indicate a putative role for Gamma Knife radiosurgery in the treatment of these patients.

Gamma Knife radiosurgery of primary and metastatic malignant brain tumors, a preliminary report.

Between February 1993 and March 1994, 75 metastases, 16 gliomas and 2 AIDS-related malignant lymphomas were treated with Gamma Knife radiosurgery. Metastatic brain tumors (54% lung cancer, 14% breast cancer, 13.5% melanoma) were the most frequent and clinically rewarding cases. So-called local control was achieved in almost all patients, the vast majority showing neurological improvement associated with radiological disappearance or dramatic shrinkage of the tumor within 9-12 weeks from treatment. According to our modified 'Pittsburgh' protocol, we have treated up to four distinct intracranial lesions, up to a total maximum volume of 20 cm3, with an average surface dose of 25 Gy, with or without additional whole brain radiotherapy (WBR). Preliminary follow-up data seem to confirm increased quality of life and survival rates. The results were particularly striking whenever primary tumors were under control, and were poorly influenced by associated WBR. Gamma Knife treatment was also performed in a selected group of patients with small-to-medium-sized, well-defined, histologically proven, cerebral gliomas. The main indications for radiosurgery were high-risk surgery, multifocal disease, ventricular seeding and unresected or recurrent tumor. The prescription doses ranged from 18 to 30 Gy, with a mean of 27 Gy. Low-grade astrocytomas (9/16 cases) showed the better clinical and radiological response to treatment, with neurological recovery and significant reduction in tumor volume within 3-5 months in 5 of the 9 patients. In 4 of 7 high-grade gliomas, there was little or no response. However, an impressive radiological regression with full clinical recovery was observed in 2 high-grade cases with small tumor volumes: a recurrent, anaplastic 'mixed glioma' of the pineal region and a double ventricular seeding of a previously operated anaplastic astrocytoma.