Comparison of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy systems.

The use of three-dimensional conformal radiation therapy (3DCRT) has now become common practice in radiation oncology departments around the world. Using beam's eye viewing of volumes defined on a treatment planning computed tomography scan, beam directions and beam shapes can be selected to conform to the shape of the projected target and minimize dose to critical normal structures. Intensity-modulated radiation therapy (IMRT) can yield dose distributions that conform closely to the three-dimensional shape of the target volume while still minimizing dose to normal structures by allowing the beam intensity to vary across those shaped fields. Predicted dose distributions for patients with tumors of the prostate, nasopharynx, and paraspinal region are compared between plans made with 3DCRT programs and those with inverse-planned IMRT programs. The IMRT plans are calculated for either static or dynamic beam delivery methods using multileaf collimators. Results of these comparisons indicate that IMRT can yield significantly better dose distributions in some situations at the expense of additional time and resources. New technologies are being developed that should significantly reduce the time needed to plan, implement, and verify these treatments. Current research should help define the future role of IMRT in clinical practice.

Comparison of radiosurgery treatment modalities based on physical dose distributions.

PURPOSE: As a means of selecting the optimal stereotactic radiosurgery (SRS) treatment modality, a comparison of physical dose distributions to defined targets and nontarget brain tissue has been made for a group of test cases selected to represent a range of treatment-planning situations from small, nearly spherical volumes to large irregular volumes. METHODS AND MATERIALS: Plans were developed for each case using photon beams from the Leksell Gamma Unit (LGU), multiarc bremsstrahlung photon beams from a linear accelerator (linac) and proton beams, with the objective of encompassing the target as closely as possible with the prescription isodose line, and minimizing dosage to normal tissue within the bounds of standard clinical practice. Dose-volume histograms (DVHs) were calculated for target and for nontarget brain tissue and compared for the various modalities. RESULTS: In general, protons delivered less dosage to normal brain than other modalities for large and peripheral lesions and LGU plans were more successful at conforming to highly irregular shapes than conventional linac plans. CONCLUSIONS: Differences were observed to depend on treatment modality, target characteristics (shape, size and location), and the amount of effort expended on treatment planning and the time allotted for treatment implementation.

Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy.

PURPOSE: To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS: All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

A dosimetric comparison of fan-beam intensity modulated radiotherapy with Gamma Knife stereotactic radiosurgery for treating intermediate intracranial lesions.

PURPOSE: To compare and evaluate treatment plans for the fan-beam intensity modulated radiotherapy and the Gamma Knife radiosurgery for treating medium-size intracranial lesions (range 4-25 cm3). METHODS AND MATERIALS: Treatment plans were developed for the Leksell Gamma Knife and a fan-beam inverse treatment planning system for intensity modulated radiotherapy. Treatment plan comparisons were carried out using dose-volume histogram (DVH), tissue-volume ratio (TVR), and maximum dose to the prescription dose (MDPD) ratio. The study was carried out for both simulated targets and clinical targets with irregular shapes and at different locations. RESULTS: The MDPD ratio was significantly greater for the Gamma Knife plans than for the fan-beam IMRT plans. The Gamma Knife plans produced equivalent TVR values to the fan-beam IMRT plans. Based on the DVH comparison, the fan-beam IMRT delivered significantly more dose to the normal brain tissue than the Gamma Knife. The results of the comparison were found to be insensitive to the target locations. CONCLUSION: The Gamma Knife is better than the fan-beam IMRT in sparing normal brain tissue while producing equivalent tumor dose conformity for treating medium-size intracranial lesions. However, the target dose homogeneity is significantly better for the fan-beam IMRT than for the Gamma Knife.

Precise positioning of patients for radiation therapy.

We have developed a number of immobilization schemes which permit precise daily positioning of patients for radiation therapy. Pretreatment and post-treatment radiographs have been taken with the patient in the treatment position and analyzed to determine the amount of intratreatment movement. Studies of patients in the supine, seated and decubitus positions indicate mean movements of less than 1 mm with a standard deviation of less than 1mm. Patients immobilized in the seated position with a bite block and a mask have a mean movement of about 0.5 mm +/- 0.3 mm (s.d.), and patients immobilized in the supine position with their necks hyperextended for submental therapy evidence a mean movement of about 1.4 mm +/- 0.9 mm (s.d.). With the exception of those used for the decubitus position, the immobilization devices are simply fabricated out of thermoplastic casting materials readily available from orthopedic supply houses. A study of day-to-day reproducibility of patient position using laser alignment and pretreatment radiographs for final verification of position indicates that the initial laser alignment can be used to position a patient within 2.2 mm +/- 1.4 mm (s.d.) of the intended position. These results indicate that rigid immobilization devices can improve the precision of radiotherapy, which would be advantageous with respect to both tumor and normal tissue coverage in certain situations.

Comparison of treatment plans involving intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with conventional treatment plans for a case of locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: The study case was planned using two types of IMRT techniques, as well as a three-dimensional conformal radiotherapy technique (3D-CRT), and a traditional treatment method using bilateral opposing fields. These four plans were compared with respect to dose conformality, dose-volume histogram (DVH), dose to the sensitive normal tissue structures, and ease of treatment delivery. RESULTS: The planned dose distributions were more conformal to the tumor target volume in the IMRT plans than those in the conventional plans. With similar dose coverage of the clinical target volume (CTV), defined as delivery of minimum of 60 Gy to >/= 95% of CTV, the IMRT plans achieved better sensitive normal tissue structure sparing, while concomitantly delivering a minimum dose of 68 Gy to >/= 95% of the gross tumor volume (GTV) at a higher dose per fraction. CONCLUSIONS: Compared to conventional techniques, IMRT techniques provide improved tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced nasopharyngeal carcinoma. With improvement of the delivery efficiency, IMRT should provide the optimal treatment for all nasopharyngeal carcinoma. Further studies are needed to establish the true clinical advantage of this new modality.

Dose optimization for the treatment of anaplastic thyroid carcinoma: a comparison of treatment planning techniques.

PURPOSE: To evaluate and compare dose optimization for the treatment of anaplastic thyroid carcinoma using a 3D conformal plan, and two 3D intensity-modulated inverse plans. METHODS AND MATERIALS: After patient immobilization using an alpha cradle and head-mask system, a postoperative CT scan was obtained to delineate the gross tumor volume (GTV), the clinical tumor volume (CTV), and adjacent critical structures. Treatment plans were generated using UM-Plan (University of Michigan), PeacockPlan and Corvus (NOMOS Corporation, Sewickley, PA). Isodoses were displayed in the sagittal, coronal, and multiple axial planes, and dose-volume histograms (DVH) were generated for the GTV, CTV, and critical normal tissues. Treatment times were estimated to compare the practicality of delivering each plan in a busy radiotherapy department. RESULTS: All three treatment planning systems were able to deliver a minimum dose of 60 Gy to the GTV while keeping the maximum spinal cord dose at or below 45 Gy. However, there were differences in the doses delivered to 50% and 5% of the cord, the minimum CTV dose, and the overall treatment time. The PeacockPlan best spared the uninvolved tissues of the posterior neck, and provided the lowest dose to the cord without compromising the CTV. CONCLUSIONS: Inverse treatment planning provides superior dose optimization for the treatment of anaplastic thyroid carcinoma. The radiobiologic impact of intensity modulation for this tumor should be further tested clinically.

Conservative treatment of uveal melanoma: local recurrence after proton beam therapy.

Twenty-three of 1006 (2.3%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986 received additional treatment for documented (15 patients) or suspected (eight patients) tumor growth in the irradiated eye. Growth within the initially irradiated volume was documented at Massachusetts Eye and Ear Infirmary in 12 patients. Documented growth occurred in nine of 665 (1.4%) patients with small and intermediate size tumors, at times after treatment ranging from 6 to 48 months (median 16 months), and in three of 341 (.9%) patients with large tumors at 7, 11, and 12 months after treatment. Melanoma growing totally outside the treated volume was also documented in three additional patients at 7, 9, and 45 months; two of these were thought to be "ring melanomas". Eight patients had the treated eye removed elsewhere for suspected tumor growth. The additional treatment in these 23 patients was conservative in nine patients (repeat proton irradiation in five and laser photocoagulation in four). Thirteen underwent immediate enucleation and one had orbital exenteration. Ultimately, 17 of the 23 eyes (74%) were removed. Estimated probability of local control of the melanoma within the irradiated eye at 60 months was 96.3 +/- 1.5%. Dose distributions to the 12 patients with documented local failure within the irradiated volume were analyzed. Ten tumors recurred marginally in an area receiving less than the prescribed dose of 70 CGE (CGE = Cobalt Gray Equivalents = proton Gy X RBE 1.1), whereas only two recurred in the volume receiving full dose. Based on these data, it appears that a dose of 70 CGE in five fractions is associated with very high rates of local control in human uveal melanoma. It is reasonable to consider initiating studies using a lower total dose or a more protracted course, to determine if some of the observed complications are dose-related.

Relative biological effectiveness of modulated proton beams in various murine tissues.

The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience.

PURPOSE: To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION: 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma.

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.

PURPOSE: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. METHODS AND MATERIALS: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. RESULTS: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2 patients (28 vs. 45%) and also for those with well and moderately differentiated tumors versus poorly differentiated tumors (32 and 50%). These differences were not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs. 12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1 versus arm 2. CONCLUSIONS: An increase in prostate tumor dose by external beam of 12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of 67.2 Gy by a photon boost significantly improved local control only in patients with poorly differentiated tumors. It has increased late radiation sequelae, and as yet, has not increased overall survival, disease-specific survival, or total recurrence-free survival in any subgroup. These results have led us to test by a subsequent Phase III trial the potential beneficial effect on local control and disease-specific survival of a 12.5% increase in total dose relative to conventional dose in patients with T1, T2a, and T2b tumors.

MR-spectroscopy guided target delineation for high-grade gliomas.

PURPOSE: Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a reliable indicator of active and microscopic disease in malignant brain tumors. We assessed the impact MRSI might have on the target volumes used for radiation therapy treatment planning for high-grade gliomas. METHODS AND MATERIALS: Thirty-four patients (22 Grade III; 12 Grade IV astrocytomas) were evaluated; each had undergone MRI and MRSI studies before surgery. MRI data sets were contoured for T1 region of contrast enhancement (T1), region of necrosis, and T2 region of hyperintensity (T2). The three-dimensional MRSI peak parameters for choline (Cho) and N-acetylaspartate (NAA), acquired by a multivoxel technique, were categorized based on an abnormality index (AI), a quantitative assessment of tissue metabolite levels. The AI data were aligned to the MRI and displayed as three-dimensional contours. AI vs. T conjoint and disjoint volumes were compared. RESULTS: For both grades, although T2 estimated the region at risk of microscopic disease as being as much as 50% greater than by MRSI, metabolically active tumor still extended outside the T2 region in 88% of patients by as many as 28 mm. In addition, T1 suggested a lesser volume and different location of active disease compared to MRSI. CONCLUSION: The use of MRSI to define target volumes for RT treatment planning would increase, and change the location of, the volume receiving a boost dose as well as reduce the volume receiving a standard dose. Incorporation of MRSI into the treatment-planning process may have the potential to improve control while reducing complications.

Dose conformity of gamma knife radiosurgery and risk factors for complications.

PURPOSE: To quantitatively evaluate dose conformity achieved using Gamma Knife radiosurgery, compare results with those reported in the literature, and evaluate risk factors for complications. METHODS AND MATERIALS: All lesions treated at our institution with Gamma Knife radiosurgery from May 1993 (when volume criteria were routinely recorded) through December 1998 were reviewed. Lesions were excluded from analysis for reasons listed below. Conformity index (the ratio of prescription volume to target volume) was calculated for all evaluable lesions and for lesions comparable to those reported in the literature on conformity of linac radiosurgery. Univariate Cox regression models were used to test for associations between treatment parameters and toxicity. RESULTS: Of 1612 targets treated in 874 patients, 274 were excluded, most commonly for unavailability of individual prescription volume data because two or more lesions were included within the same dose matrix (176 lesions), intentional partial coverage for staged treatment of large arteriovenous malformations (AVMs) (33 lesions), and missing target volume data (26 lesions). The median conformity indices were 1.67 for all 1338 evaluable lesions and 1.40-1.43 for lesions comparable to two linac radiosurgery series that reported conformity indices of 1.8 and 2.7, respectively. Among all 651 patients evaluable for complications, there were one Grade 5, eight Grade 4, and 27 Grade 3 complications. Increased risk of toxicity was associated with larger target volume, maximum lesion diameter, prescription volume, or volume of nontarget tissue within the prescription volume. CONCLUSIONS: Gamma Knife radiosurgery achieves much more conformal dose distributions than those reported for conventional linac radiosurgery and somewhat more conformal dose distributions than sophisticated linac radiosurgery techniques. Larger target, nontarget, or prescription volumes are associated with increased risk of toxicity.

Evaluation of ultrasound-based prostate localization for image-guided radiotherapy.

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment. Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed. On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively. In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.

Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control.

PURPOSE: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). METHODS AND MATERIALS: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. RESULTS: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). CONCLUSION: A minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin.

Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid], and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of 137Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shown for anesthetized, air-breathing animals.

Multileaf collimator leaf sequencing algorithm for intensity modulated beams with multiple static segments.

The "stop and shoot" method of producing intensity modulation using combinations of static multileaf collimator (MLC) segments has a number of advantages including precise dose delivery, easy verification, and general availability. However, due to the potential limitation of prolonged treatment time, it is essential to keep the number of required segments to a reasonable number. We propose an algorithm to minimize the number of segments for an intensity modulated field. In this algorithm, the sequence of delivery intensity is proposed to be a series of powers of 2, depending on the maximum intensity level in the matrix. The MLC leaf position sequence is designed directly on the two-dimensional intensity matrix to irradiate the largest possible area in each segment. The algorithm can be applied directly to MLC systems with different motion constraints. This algorithm has been evaluated by generating 1000 random 15 x 15 cm intensity matrices, each having from 3 to 16 intensity levels. Five clinical intensity modulated fields generated from the NOMOS CORVUS planning system for a complex clinical head and neck case were also tested with this and two other algorithms. The results of both the statistical and clinical studies showed that for all the intensity matrices tested, the proposed algorithm results in the smallest number of segments with a moderately increased monitor units. Thus it is well-suited for use in static MLC intensity modulation beam delivery. For MLC systems with interleaf motion constraint, we prove mathematically that this constraint reduces the tongue and groove effect at the expense of an increase of 25% in the number of segments.

Computer-assisted positioning of radiotherapy patients using implanted radiopaque fiducials.

For certain external beam radiotherapy procedures, precise alignment of patients with the treatment beam is essential for good treatment outcome. A method has been developed for quickly achieving precise patient alignment with the aid of stereoscopically located fiducial markers. The alignment algorithm is developed from standard rigid body mechanics using closed form solutions, obviating the need for iterative fitting methods. The technique is implemented with a digitizing tablet and plane film radiographs. The accuracy of alignment with this method in phantom studies is better than 1 mm and 1 deg relative to CT data. The repeatability of positioning is 0.5 mm (standard deviation) and 0.36 deg (standard deviation).

Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom.

PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.