Horacio Patrocinio

THE USE OF HYPOFRACTIONATED INTENSITY-MODULATED IRRADIATION IN THE TREATMENT OF GLIOBLASTOMA MULTIFORME: PRELIMINARY RESULTS OF A PROSPECTIVE TRIAL

PURPOSE Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM. METHODS AND MATERIALS Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume < or =110 cm3 were treated with a hypofractionated accelerated course of radiotherapy. The gross tumor volume (GTV) was defined as the contrast-enhancing lesion on the postoperative MRI T1-weighted images with the latter fused with computed tomography images for treatment planning. The planning target volume was defined as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases. RESULTS Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival rate was 40%, and the median progression-free survival was 5.2 months (range: 1.9-12.8 months). CONCLUSION This hypofractionated accelerated irradiation schedule using forward planning (step-and-shoot) hypofractionated, intensity-modulated accelerated radiotherapy is feasible and seems to be a safe treatment for patients with GBM. A 2-week reduction in the treatment time may be of valuable benefit for this group of patients. However, despite this accelerated regimen, no survival advantage has been observed.

Physical aspects of dynamic stereotactic radiosurgery with very small photon beams (1.5 and 3 mm in diameter).

Stereotactic radiosurgery is often used for treating functional disorders. For some of these disorders, the size of the target can be on the order of a millimeter and the radiation dose required for treatment on the order of 80 Gy. The very small radiation field and high prescribed dose present a difficult challenge in beam calibration, dose distribution calculation, and dose delivery. In this work the dose distribution for dynamic stereotactic radiosurgery, carried out with 1.5 and 3 mm circular fields, was studied. A 10 MV beam from a Clinac-18 linac (Varian, Palo Alto, CA) was used as the radiation source. The BEAM/EGS4 Monte Carlo code was used to model the treatment head of the machine along with the small-field collimators. The models were validated with the EGSnrc code, first through a calculation of percent depth doses (PDD) and dose profiles in a water phantom for the two small stationary circular beams and then through a comparison of the calculated with measured PDD and profile data. The three-dimensional (3-D) dose distributions for the dynamic rotation with the two small radiosurgical fields were calculated in a spherical water phantom using a modified version of the fast XVMC Monte Carlo code and the validated models of the machine. The dose distributions in a horizontal plane at the isocenter of the linac were measured with low-speed radiographic film. The maximum sizes of the Monte Carlo-calculated 50% isodose surfaces in this horizontal plane were 2.3 mm for the 1.5 mm diameter beam and 3.8 mm for the 3 mm diameter beam. The maximum discrepancies between the 50% isodose surface on the film and the 50% Monte Carlo-calculated isodose surfaces were 0.3 mm for both the 1.5 and 3 mm beams. In addition, the displacement of the delivered dose distributions with respect to the laser-defined isocenter of the machine was studied. The results showed that dynamic radiosurgery with very small beams has a potential for clinical use.

Development of a Monte Carlo model for the Brainlab microMLC

Stereotactic radiosurgery with several static conformal beams shaped by a micro multileaf collimator (microMLC) is used to treat small irregularly shaped brain lesions. Our goal is to perform Monte Carlo calculations of dose distributions for certain treatment plans as a verification tool. A dedicated microMLC component module for the BEAMnrc code was developed as part of this project and was incorporated in a model of the Varian CL2300 linear accelerator 6 MV photon beam. As an initial validation of the code, the leaf geometry was visualized by tracing particles through the component module and recording their position each time a leaf boundary was crossed. The leaf dimensions were measured and the leaf material density and interleaf air gap were chosen to match the simulated leaf leakage profiles with film measurements in a solid water phantom. A comparison between Monte Carlo calculations and measurements (diode, radiographic film) was performed for square and irregularly shaped fields incident on flat and homogeneous water phantoms. Results show that Monte Carlo calculations agree with measured dose distributions to within 2% and/or 1 mm except for field size smaller than 1.2 cm diameter where agreement is within 5% due to uncertainties in measured output factors.

STEREOTACTIC FRACTIONATED RADIOTHERAPY IN THE TREATMENT OF JUXTAPAPILLARY CHOROIDAL MELANOMA: THE MCGILL UNIVERSITY EXPERIENCE

PURPOSE To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. METHODS AND MATERIALS We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. RESULTS The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. CONCLUSIONS Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

Accelerated radiotherapy with simultaneous integrated boost fractionation and intensity-modulated radiotherapy for advanced head and neck cancer

Objective To determine the feasibility and toxicity profile of accelerated radiotherapy with a simultaneous integrated boost fractionation scheme with intensity-modulated radiotherapy (SIB-IMRT) with or without chemotherapy. Study Design And Setting Forty-nine patients with advanced head and neck cancer underwent SIB-IMRT. Concomitant chemotherapy was administered in 29 patients. Results Grade 3 acute toxicities included 55% mucositis, 20% odynophagia, 12% nausea, 18% hematologic, and 8% skin. There were no grade 4 toxicities or treatment-related deaths. With a median follow-up of 25 months, locoregional control was 83%, and overall survival was 80%. Of patients with grade 3 late toxicities, two patients (4% of the total) required a permanent percutaneous endoscopic gastrostomy tube, and osteonecrosis occurred in one patient (2% of the total). Conclusions SIB-IMRT is a feasible technique that shortens the overall treatment time in the radical treatment of patients with advanced head and neck cancer while maintaining acceptable rates of acute toxicity in this study. Although the results are promising, this approach should be considered only in the setting of a clinical trial.

Stereotactic radiosurgery in the management of angiographically occult vascular malformations.

PURPOSE To evaluate the role of stereotactic radiosurgery in the treatment of angiographically occult vascular malformations (AOVMs). METHODS AND MATERIALS From 1987 to 1996, 21 patients, 10 males and 11 females, median age of 41 years (range: 7-75 years), with an intracerebral AOVM underwent stereotactic radiosurgery at our institution. All were considered at high risk for surgical intervention. The vascular lesions were located in the brainstem (17 patients), basal ganglia (2), occipital lobe (1), and cerebellum (1). Diagnosis was based on high-resolution magnetic resonance imaging (MRI). Clinical presentation at onset included previous intracerebral hemorrhage (20 patients) and epilepsy (1). All patients were treated with a linac-based radiosurgical technique. The median dose delivered was 25 Gy (range 13-50 Gy), typically prescribed to the 80-90% isodose surface (range 50-90%), which corresponded to the periphery of the vascular malformation. Patients were followed by clinical neurologic assessment and by MRI on a regular interval basis. RESULTS Follow-up was obtained in 20 patients; clinical or MRI information was not available for 1 patient, and this patient was excluded from our analysis. At a median follow-up of 77 months (range: 4-141 months), follow-up MRIs postradiosurgery do not demonstrate any changes in the appearance of the AOVM. Four patients developed an intracranial bleed at 4, 8, 35, and 57 months postradiosurgery. Annual hemorrhage rates were considerably higher in the observation period preradiosurgery than postradiosurgery (30% vs. 3.2%, p < 0.001). Complications postradiosurgery were observed in 4 patients. Three patients developed mild to moderate edema surrounding the radiosurgical target, expressed at 5, 8, and 24 months, respectively. In all cases, the edema was transient and resolved completely on subsequent MRIs. One of the 4 patients developed radiation necrosis 8 months after radiosurgery. CONCLUSION The use of stereotactic radiosurgery in the treatment of AOVM continues to be controversial. Our results appear to show a reduction in the risk of symptomatic hemorrhage post treatment. Patients with previous history of hemorrhage or progressive neurologic deficit and small, well circumscribed lesions may benefit from a trial of stereotactic radiosurgery.

An alternative mantle irradiation technique using 3D CT- based treatment planning for female patients with Hodgkin’s disease

PURPOSE For female patients, radiotherapy treatment for Hodgkins disease invariably results in the irradiation of breast tissue that may lead to radiation induced secondary cancers. The risk for secondary breast cancer is correlated with dose. We have developed a technique in an attempt to increase breast sparing during mantle field irradiation for female patients. MATERIAL AND METHODS To minimize the irradiated breast volume, a virtual simulation technique making use of a Styrofoam breast immobilization board has been developed whereby the patient lies prone with the breasts positioned in grooves within the board. The breast position is adjusted using Styrofoam wedges, and breast placement is verified using an AP CT-pilot view. A CT scan of the neck and thoracic regions is taken, and the lymph nodes, breast volume and critical structures are outlined. Virtual simulation of the mantle fields (typically AP/PA isocentric beams) is performed, and beam blocks are drawn on the digitally reconstructed radiographs (DRR) generated by the virtual simulation package. The shielding is designed to allow adequate margins around the lymph nodes while maximizing shielding of the lung and breast tissues. The para-aortic fields are also easily determined through virtual simulation, where multi-planar reconstructions (MPR) and 3D renderings of the patients CT data are used to determine the field limits and beam gaps. In addition to allowing for the geometric optimization of the positioning of the breasts under the lung shields, the virtual simulation technique provides the necessary information for a 3D dosimetric analysis, including dose-volume histograms (DVHs) of the irradiated breast volume. RESULTS The 3D breast sparing technique was qualitatively and quantitatively compared to non-CT-based techniques and other 3D techniques currently available to assess the protection of the breasts. In a preliminary analysis, virtual simulation images (DRRs, 3D rendering and multi-planar reconstruction) demonstrated the advantage of using the breast sparing technique. A further analysis of DVHs showed a reduction of at least 50% in the volume of breast tissue irradiated when using the breast positioning board and virtual simulation as compared to the conventional simulation techniques where a breast immobilization board was not used. CONCLUSIONS The use of a breast immobilization board and of a virtual simulation technique is recommended for the planning and treatment of female patients with Hodgkins disease. DVH analysis has shown that this leads to a decrease in the volume of breast irradiated. It is hoped that this approach will reduce the risk of secondary breast malignancies in female patients with Hodgkins disease.

Limiting values of backscatter factors for low-energy x-ray beams

Models for the calculation of upper and lower limiting values to the backscatter factor (BSF) are presented. The upper limit is obtained from Monte Carlo simulations of infinite parallel beams incident on semi-infinite phantoms with the dose contributions from all orders of photon scatter considered. The lower limits are calculated using an analytical photon transport model which considers only the primary dose and the scatter dose from photons that have undergone single scattering interactions in the phantom. The limiting values can be used to evaluate measured and modelled BSF values for x-ray beams with photons of < or = 150 keV. A parametrization of the limiting values in terms of photon energy and irradiation field size is presented so that results determined for monoenergetic beams can be extended to polyenergetic spectra. The utility of the limits is illustrated by comparisons made with BSFs from the literature.

Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiation Therapy in the Treatment of Intermediate-Risk Prostate Cancer – Long Term Results

PURPOSE We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). METHODS AND MATERIALS Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. RESULTS The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. CONCLUSION The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.

Prostate gland edema after single-fraction high-dose rate brachytherapy before external beam radiation therapy

PURPOSE High-dose rate brachytherapy (HDRB) is frequently used as a boost to external beam radiation therapy (EBRT) in prostate cancer patients. With the increasing use of small planning target volume margins in EBRT, prostatic edema induced by HDRB can be a contributing factor to geometric miss when HDRB is performed before or during EBRT. We assessed prostate gland volumetric change after single-fraction HDRB and its impact on definition of treatment volume for EBRT. METHODS AND MATERIALS Thirty-one consecutive patients with intermediate-risk prostate cancer treated with single-fraction HDRB (10 Gy) combined with hypofractionated EBRT were analyzed. A second CT scan was performed 7 days after HDRB, and images were coregistered with the planning CT scan that contained the original clinical target volume (CTV). The post-HDRB prostate CTV volume was compared with the original CTV by a single observer. RESULTS All patients presented volumetric variation. In most cases (68%), the prostate increased in volume, whereas it decreased in 32%. The mean prostatic volume was 42.2 cc before HDRB and 43.6 cc after HDRB, representing a mean volume difference of 3.4%, ranging from -14.2% to 23.8% (p=0.756). This difference is the result of mean changes of 0.6mm (-6.1 to 6.6) in the anterior-posterior, 0.5mm (-5.5 to 3.0) in the lateral, and 0.2mm (-5.0 to 5.0) in the superior-inferior axes. CONCLUSIONS Although a nonsignificant volumetric change occurs after single-fraction HDRB, individual variations on specific axis could lead to important uncertainties during EBRT.