Francis J. Bova

Radiation optic neuropathy after megavoltage external-beam irradiation : analysis of time-dose factors

PURPOSE To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. RESULTS Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of > or = 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of > or = 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47% when given in fraction sizes of > or = 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. CONCLUSION As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.

A re-evaluation of split-course technique for squamous cell carcinoma of the head and neck

Abstract Therapeutic results of split-course vs. continuous-course external beam irradiation were analyzed retrospectively in 468 consecutive patients with squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, and supraglottic larynx who were treated with curative intent at the University of Florida between September 1964 and August 1976. 214 patients received split-course treatment and 254 were treated by the continuous-course method. Except for the planned 14–16 day interruption after 2820–3000 rad in the split-course group, the techniques and total doses of irradiation did not differ. Local control was poorer for all T-stages in patients who were treated by the split-course technique. Control of neck disease by irradiation alone was also poorer among split-course irradiation patients. For each stage of disease, patients who received continuous-course irradiation had approximately 10% higher 5-year survival rates than patients who were treated by the split-course technique. The rate of development of late radiation complications was similar for the 2 treatment techniques. Routine use of the split-course technique has been discontinued since the dose required to compensate for the rest interval is unknown.

The effects of irradiation on the eye and optic nerve

Abstract Late effects of irradiation of the eye and optic nerve in 74 patients are reviewed. Time-dose analyses are performed for lacrimal apparatus, retinal, and optic nerve injuries. Management of radiation complications is discussed. Recommendations are made regarding radiation treatment techniques and methods of reducing the risk of late injury.

Prognostic and treatment factors affecting pelvic control of Stage IB and IIA-B carcinoma of the intact uterine cervix treated with radiation therapy alone.

This is a retrospective analysis of 264 patients with Stage IB and IIA‐B carcinoma of the cervix treated with curative intent at the University of Florida from October 1964 through April 1980. There is a minimum 2‐year follow‐up. Patients dead of distant metastases (13), dead from intercurrent disease (14), or lost to follow‐up (1) less than 24 months from treatment with pelvic disease controlled were excluded from analysis of pelvic control. All patients were included in analysis of complications and survival. Tumor size and hematocrit were noted to be significant prognostic factors with regard to control of disease in the pelvis in Stage IB and IIA cancers. Tumor size and hematocrit also influenced pelvic control in Stage IIB, but to a lesser extent than in Stages IB and IIA. Patient age was a weak prognostic factor for control of disease in the pelvis for Stages IB, IIA, and IIB, but more strongly influenced pelvic control when considered in conjunction with tumor size and hematocrit. Overall treatment time influenced pelvic control in all cases when the size of the lesion was ≧6 cm. in lesions ≧6 cm in diameter, the amount of tumor regression noted at the time of the radium application after 3500 to 4000 rad external beam irradiation was a predictor of pelvic control. Data on treatment complications and survival are included, and future treatment strategies discussed.

Calibration of three-dimensional ultrasound images for image-guided radiation therapy

A new technique of patient positioning for radiotherapy/radiosurgery of extracranial tumours using three-dimensional (3D) ultrasound images has been developed. The ultrasound probe position is tracked within the treatment room via infrared light emitting diodes (IRLEDs) attached to the probe. In order to retrieve the corresponding room position of the ultrasound image, we developed an initial ultrasound probe calibration technique for both 2D and 3D ultrasound systems. This technique is based on knowledge of points in both room and image coordinates. We first tested the performance of three algorithms in retrieving geometrical transformations using synthetic data with different noise levels. Closed form solution algorithms (singular value decomposition and Horns quaternion algorithms) were shown to outperform the Hooke and Jeeves iterative algorithm in both speed and accuracy. Furthermore, these simulations show that for a random noise level of 2.5, 5, 7.5 and 10 mm, the number of points required for a transformation accuracy better than 1 mm is 25, 100, 200 and 500 points respectively. Finally, we verified the tracking accuracy of this system using a specially designed ultrasound phantom. Since ultrasound images have a high noise level, we designed an ultrasound phantom that provides a large number of points for the calibration. This tissue equivalent phantom is made of nylon wires, and its room position is optically tracked using IRLEDs. By obtaining multiple images through the nylon wires, the calibration technique uses an average of 300 points for 3D ultrasound volumes and 200 for 2D ultrasound images, and its stability is very good for both rotation (standard deviation: 0.4 degrees) and translation (standard deviation: 0.3 mm) transformations. After this initial calibration procedure, the position of any voxel in the ultrasound image volume can be determined in world space, thereby allowing real-time image guidance of therapeutic procedures. Finally, the overall tracking accuracy of our 3D ultrasound image-guided positioning system was measured to be on average 0.2 mm, 0.9 mm and 0.6 mm for the AP, lateral and axial directions respectively.

Linear accelerator-based stereotactic radiosurgery for acoustic Schwannomas☆

PURPOSE Stereotactic radiosurgery (SRS) is currently being investigated for treatment of acoustic schwannomas in patients who are not good surgical candidates. The vast majority of the available data is based on gamma knife-treated patients. We present the largest series of patients treated with linear accelerator-based SRS. METHODS AND MATERIALS Thirty-two patients with acoustic schwannomas were treated with SRS between July 1988 and February 1993; follow-up ranged from 4-59 months. Age ranged from 34-88 years (mean, 62 years). The primary presenting symptom was hearing loss in 30 patients and dementia in two patients. Indications for SRS were age > 65 years (17 patients); recurrence after surgery (13 patients); and medical infirmity (two patients). Dose to the periphery of the lesion ranged from 10-22.5 Gy (mean, 15.5 Gy) specified at the 68-90% isodose line (mean, 80%). Collimator size ranged from 12-35 mm (mean, 23 mm), indicating that the sizes of the tumors were significantly larger than those reported in most gamma knife series. RESULTS Follow-up magnetic resonance imaging (MRI) and/or computed tomography (CT) scans revealed the following at 1 year: tumor regression, 12 patients (63%); and no change, seven patients (37%). At 2 years, 11 tumors (73%) were smaller and four tumors (27%) were unchanged. At 3 years, seven patients (78%) had experienced tumor regression and two (22%) had no change. No patient experienced tumor progression after SRS. Seven patients (22%) suffered one or more treatment complications: new onset of 5th and/or 7th cranial nerve deficit (six patients), ataxia (two patients), and/or hydrocephalus necessitating VP shunt (two patients). CONCLUSION Linear accelerator-based SRS provides excellent short-term local control and a relatively low incidence of complications for acoustic schwannomas. Our data compare favorably with results obtained with gamma knife-based SRS. Additional follow-up will be necessary to evaluate the long-term results of treatment.

Potential clinical efficacy of intensity-modulated conformal therapy

PURPOSE The purpose of this study was to examine the potential benefit of using intensity-modulated conformal therapy for a variety of lesions currently treated with stereotactic radiosurgery or conventional radiotherapy. METHODS AND MATERIALS Intensity-modulated conformal treatment plans were generated for small intracranial lesions, as well as head and neck, lung, breast, and prostate cases, using the Peacock Plan treatment-planning system (Nomos Corporation). For small intracranial lesions, intensity-modulated conformal treatment plans were compared with stereotactic radiosurgery treatment plans generated for patient treatment at the University of Florida Shands Cancer Center. For other sites (head and neck, lung, breast, and prostate), plans generated using the Peacock Plan were compared with conventional treatment plans, as well as beams-eye-view conformal treatment plans. Plan comparisons were accomplished through conventional qualitative review of two-dimensional (2D) dose distributions in conjunction with quantitative techniques, such as dose-volume histograms, dosimetric statistics, normal tissue complication probabilities, tumor control probabilities, and objective numerical scoring. RESULTS For small intracranial lesions, there is little difference between intensity-modulated conformal treatment planning and radiosurgery treatment planning in the conformation of high isodose lines with the target volume. However, stereotactic treatment planning provides a steeper dose gradient outside the target volume and, hence, a lower normal tissue toxicity index. For extracranial sites, objective numerical scores for beams-eye-view and intensity-modulated conformal planning techniques are superior to scores for conventional treatment plans. The beams-eye-view planning technique prevents geographic target misses and better excludes healthy tissues from the treatment portal. Compared with scores for the beams-eye-view planning technique, scores for intensity-modulated conformal plans using the Peacock Plan were significantly better for the lung and head and neck cases studied, equivalent for prostate cases, and inferior for breast cases. CONCLUSION Using the entire 3D data set to construct radiotherapy plans through virtual simulation is always advantageous, whether done for stereotactic radiosurgery, beams-eye-view conformal therapy, or intensity-modulated conformal treatment. Intensity modulation of the photon beam further enhances treatment planning under specific conditions. In general, the intensity-modulated technique is advantageous for large, irregular targets with critical structures in close proximity. Intensity-modulated treatment planning does not appear advantageous for stereotactic radiosurgery or treatment of the intact breast.

Preliminary experience with frameless stereotactic radiotherapy

PURPOSE To report initial clinical experience with a novel high-precision stereotactic radiotherapy system. METHODS AND MATERIALS Sixty patients ranging in age from 2 to 82 years received a total of 1426 treatments with the University of Florida frameless stereotactic radiotherapy system. Of the total, 39 (65%) were treated with stereotactic radiotherapy (SRT) alone, and 21 (35%) received SRT as a component of radiotherapy. Pathologic diagnoses included meningiomas (15 patients), low-grade astrocytomas (11 patients), germinomas (9 patients), and craniopharyngiomas (5 patients). The technique was used as means of dose escalation in 11 patients (18%) with aggressive tumors. Treatment reproducibility was measured by comparing bite plate positioning registered by infrared light-emitting diodes (IRLEDs) with the stereotactic radiosurgery reference system, and with measurements from each treatment arc for the 1426 daily treatments (5808 positions). We chose 0.3 mm vector translation error and 0.3 degrees rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS With a mean follow-up of 11 months, 3 patients had recurrence of malignant disease. Acute side effects were minimal. Of 11 patients with low grade astrocytomas, 4 (36%) had cerebral edema and increased enhancement on MR scans in the first year, and 2 required steroids. All had resolution and marked tumor involution on follow-up imaging. Bite plate reproducibility was as follows. Translational errors: anterior-posterior, 0.01 +/- 0.10; lateral, 0.02 +/- 0.07; axial, 0.01 +/- 0.10. Rotational errors (degrees): anterior-posterior, 0.00 +/- 0.03; lateral, 0.00 +/- 0.06; axial, 0.01 +/- 0.04. No patient treatment was delivered beyond the maximum tolerated misalignment. Daily treatment was delivered in approximately 15 min per patient. CONCLUSION Our initial experience with stereotactic radiotherapy using the infrared camera guidance system was good. Patient selection and treatment strategies are evolving rapidly. Treatment accuracy was the best reported, and the treatment approach was practical.

Commissioning and quality assurance of an optically guided three-dimensional ultrasound target localization system for radiotherapy

Recently, there has been proliferation of image-guided positioning systems for high-precision radiation therapy, with little attention given to quality assurance procedures for such systems. To ensure accurate treatment delivery, errors in the imaging, localization, and treatment delivery processes must be systematically analyzed. This paper details acceptance tests for an optically guided three-dimensional (3D) ultrasound system used for patient localization. While all tests were performed using the same commercial system, the general philosophy and procedures are applicable to all systems utilizing image guidance. Determination of absolute localization accuracy requires a consistent stereotactic, or three-dimensional, coordinate system in the treatment planning system and the treatment vault. We established such a coordinate system using optical guidance. The accuracy of this system for localization of spherical targets imbedded in a phantom at depths ranging from 3 to 13 cm was determined to be (average +/- standard deviation) AP = 0.2 +/- 0.7 mm, Lat = 0.9 +/- 0.6 mm, Ax = 0.6 +/- 1.0 mm. In order to test the ability of the optically guided 3D ultrasound localization system to determine the magnitude of an internal organ shift with respect to the treatment isocenter, a phantom that closely mimics the typical human male pelvic anatomy was used. A CT scan of the phantom was acquired, and the regions of interest were contoured. With the phantom on the treatment couch, optical guidance was used to determine the positions of each organ to within imaging uncertainty, and to align the phantom so the plan and treatment machine coordinates coincided. To simulate a clinical misalignment of the treatment target, the phantom was then shifted by different precise offsets, and an experimenter blind to the offsets used ultrasound guidance to determine the magnitude of the shifts. On average, the magnitude of the shifts could be determined to within 1.0 mm along each axis.

Linear accelerator radiosurgery for nonacoustic schwannomas

Abstract Purpose: To analyze the results of nonacoustic schwannomas treated with linear accelerator stereotactic radiosurgery. Methods and Materials: Between August 1989 and October 1997, 18 patients with nonacoustic schwannomas underwent stereotactic radiosurgery at the University of Florida. Nine patients had schwannomas located in the jugular foramen region, seven in the trigeminal nerve, and two in the facial nerve. Nine patients had initial subtotal resections and nine did not undergo surgical intervention. One of the 9 patients with subtotal resection was treated with radiosurgery for a recurrent tumor. Tumor volumes ranged from 0.7 to 15.4 cm 3 with a mean volume of 5.5 cm 3 . Minimal tumor doses ranged from 10.0 to 15.0 Gy with a mean dose of 13.1 Gy. Treatment dose was specified to the 80% isodose shell in 11 patients (58%) and to the 70% isodose shell in the remaining patients. Ten patients (56%) were treated with a single isocenter, 6 patients (33%) with 2–4 isocenters, and 2 patients (11%) with greater than 5 isocenters. Follow-up ranged from 5 to75 months and the mean follow-up was 32 months. Ten patients (56%) had follow-up beyond 2 years and none were lost to follow-up. Local control was defined as clinically stable neurological status and/or stable or decreased tumor size on yearly follow-up MR imaging. Results: Eighteen evaluable patients (100%) had local control after treatment. All were alive and progression-free at last follow-up. Six of 10 patients with follow-up MRI 2 years or more after treatment had tumor regression and 4 patients had stable disease. Three additional patients with an MRI at 1 year showed no tumor change. Four complications in 3 patients included one worsening of a preexisting VII nerve palsy, 2 patients with new onset of hearing loss, and one with ataxia. No surgical intervention or prolonged steroid use was necessary for any patient with complications. Five patients had improvement in preexisting neurologic deficits. Conclusions: Excellent preliminary tumor control rates and a favorable toxicity profile support the effectiveness of linear accelerator stereotactic radiosurgery for patients with nonacoustic schwannomas.