LETd Optimization Verification With an SOI Microdosimeter.

PURPOSE: A first of its kind experimental verification of dose-averaged linear energy transfer (LETd) optimized treatment plans for proton therapy has been carried out using a silicon-on-insulator microdosimeter at the Massachusetts General Hospital (MGH), Boston, USA. METHODS AND MATERIALS: Three clinical treatment plans of a typical ependymoma structure set were designed using the standard clinical approach, the proposed protocol approach, and a one-field approach. The plans were then reoptimized to reduce the LETd-weighted dose in the brain stem. All six plans were delivered in a solid water phantom and the experimental yD‾ measured. RESULTS: After LETd optimization, a reduction in yD‾ was found within the brain stem by an average of 12%, 19%, and 4% for the clinical, protocol, and one-field plans, respectively, while maintaining adequate coverage of the tumor structure. The experimental LETd-weighted doses were in agreement with the treatment planning system calculations and Monte Carlo simulations and reinforced the improvement of the optimization. CONCLUSIONS: This work demonstrates the first experimental verification of the clinical implementation of LETd optimization for patient treatment with proton therapy.

Implementation of apertures in a proton pencil-beam dose algorithm.

The use of field-specific apertures, routine in scattered or uniform-scanned proton fields, are still a necessity in pencil-beam scanned (PBS) fields to sharpen the penumbral edge at low energies and in high fraction dose application beyond that achievable with small spot size. We describe a model implemented in our clinical pencil-beam algorithm that models the insertion of a shaped aperture, including shapes adapted per energy layer such as may be achieved with a multi-leaf collimator. The model decomposes the spot transport into discrete steps. The first step transport a uniform intensity field of high-resolution sub-pencil-beams at the layer energy through the medium. This transport only considers primary scattering in both the patient and an optional range-shifter. The second step models the aperture areas and edge penumbral transition as a modulation of the uniform intensity. The third step convolves individual steps over the uniform-transported field including the aperture-modified intensities. We also introduce an efficient model based on a Clarkson sector integration for nuclear scattered halo protons. This avoids the explicit modeling of long range halo protons to the detriment of computational efficiency in calculation and optimization. We demonstrate that the aperture effect is primarily due to in-patient and shifter scattering with a small contribution from the apparent beam source position. The model provides insight into the primary physics contributions to the penumbra and the nuclear halo. The model allowed us to fully deploy our PBS capacity at our two-gantry center without which PBS treatments would have been inferior compared to scattered fields with apertures. Finally, Monte Carlo calculations have (nearly) replaced phenomenological pencil-beam models for collimated fields. Phenomenological models do, however, allow exposition of underlying clinical phenomena and closer connection to representative clinical observables.

Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery.

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

Characterization of a mini-multileaf collimator in a proton beamline.

A mini-multileaf collimator (MMLC) was mounted as a field shaping collimator in a proton beamline at the Massachusetts General Hospital. The purpose is to evaluate the device's dosimetric and mechanical properties for the use in a proton beamline. For this evaluation, the authors compared MMLC and brass aperture shaped dose distributions with regard to lateral and depth dose properties. The lateral fall off is generally broader with the MMLC, with difference varying with proton range from 0.2 to 1.2 mm. Central axis depth dose curves did not show a difference in peak-to-entrance ratio, peak width, distal fall off, or range. Two-dimensional dose distributions to investigate the conformity of MMLC shaped doses show that the physical leaf width of approximately 2.5 mm does not have a significant impact. All differences seen in dose distribution shaped by the MMLC versus brass apertures were shown to be clinically insignificant. Measured neutron doses of 0.03-0.13 mSv/Gy for a closed brass beam block (depending on range) are very low compared to the previously published data. Irradiation of the tungsten MMLC, however, produced 1.5-1.8 times more neutrons than brass apertures. Exposure of the staff resulting from activation of the device is below regulatory limits. The measurements established an equivalency between aperture and MMLC shaped dose distributions.

Impact of spot size variations on dose in scanned proton beam therapy.

BACKGROUND: In scanned proton beam therapy systematic deviations in spot size at iso-center can occur as a result of changes in the beam-line optics. There is currently no general guideline of the spot size accuracy required clinically. In this work we quantify treatment plan robustness to systematic spot size variations as a function of spot size and spot spacing, and we suggest guidelines for tolerance levels for spot size variations. METHODS: Through perturbation of spot size in treatment plans for 7 patients and a phantom, we evaluated the dose impact of systematic spot size variations of 5% up to 50%. We investigated the dependence on nominal spot size by studying scenarios with small, medium and large spot sizes for various inter-spot spacings. To come to tolerance levels, we used the Γ passing rate and dose-volume-histograms. RESULTS: Limits on spot size accuracy were extracted for 8 sites, 3 different spot sizes and 3 different inter-spot spacings. While the allowable spot size variation strongly depends on the spot size, the inter-spot spacing turned out to be only of limited influence. CONCLUSIONS: Plan robustness to spot size variations strongly depend on spot size, with small spot plans being much more robust than larger spots plans. Inter-spot spacing did not influence plan robustness. Combining our results with existing literature, we propose limits of ±25%, ±20% and ±10% of the spot width σ, for spots with σ of 2.5, 5.0 and 10 mm in proton therapy spot scanning facilities, respectively.

Impact of setup and range uncertainties on TCP and NTCP following VMAT or IMPT of oropharyngeal cancer patients.

Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models. Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario ([Formula: see text]) was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W_Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population. TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the [Formula: see text] scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W_Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W_Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W_Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W_Avg: 3%). The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods. Highlights: - TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios. - For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors. - Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%.

Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases.

BACKGROUND: The spread of systemic cancer to the brain is a common complication for cancer patients. Conventional radiotherapy offers modest palliation, and surgery is helpful only for the patient with a single metastasis in an accessible location. Stereotactic radiosurgery, a technique that permits the precise delivery of a high dose of radiation to a small intracranial target while sparing the surrounding normal brain, has been used as an alternative treatment for brain metastases. PURPOSE: Our medical center's 7-year experience with radiosurgery for metastases was reviewed to establish the effectiveness of the treatment and to understand the prognoses in patients so treated. METHODS: Retrospective analysis of hospital records, from 248 consecutive patients (421 lesions) that were treated with radiosurgery between May 1986 and May 1993, was performed. Patients were only excluded for a Karnofsky performance score of less than 70, evidence of acute neurologic deterioration, or tumor diameter more than 4 cm. Median follow-up was 26.2 months. Seventy-six percent of patients had recurrent disease, 69% had evidence of systemic disease, 69% had a single metastasis. Treatment was performed using a 6-MeV linear accelerator. The median tumor volume was 3 cm3. The median treatment dose was 1500 cGy. Whole brain radiotherapy was given to all newly diagnosed patients. Patients were followed by neurological examination and neuroimaging at regular intervals. Local control of disease was defined as a lack of progression of solid-contrast enhancement on computed tomography scan or magnetic resonance imaging. RESULTS: Median overall survival from radiosurgery was 9.4 months. The absence of active systemic disease, younger than 60 years of age, two or fewer lesions, and female sex were significantly associated with increased survival (two-sided P < .05). Actuarial local control rates were approximately 85% at 1 year and 65% at 2 years. Factors associated with a significantly decreased local control rate were location below the tentorium, recurrent tumor, and larger tumor volume (two-sided P < .05). Radioresponsive and radioresistant tumor types had similar control rates. The median drop in Karnofsky performance score at 1 year was 10%. CONCLUSIONS: The results of this retrospective analysis show that radiosurgery is an effective, minimally invasive outpatient treatment option for small intracranial metastases. Results of this study also indicate that radiosurgery not only provides local control rates equivalent to those from surgical series but is also effective in treating patients with surgically inaccessible lesions, with multiple lesions, or with tumor types that are resistant to conventional treatment.

Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma.

Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation.

The treatment of recurrent brain metastases with stereotactic radiosurgery.

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.

Radiosurgery as part of the initial management of patients with malignant gliomas.

PURPOSE: Between May 1988 and May 1991, 41 patients with malignant gliomas were enrolled onto a prospective study designed to evaluate the role of radiosurgery as a component of initial management. PATIENTS AND METHODS: Thirty-seven patients underwent radiosurgery according to the protocol and were assessable for survival and complications of treatment. Diagnoses included glioblastoma multiforme (GBM) in 23 (62%) cases and anaplastic astrocytoma in 14 (38%) cases. In 20 (54%) cases, surgical resection was attempted initially, whereas 17 (46%) patients underwent biopsy only. Patients in the study group received external-beam radiotherapy that consisted of 5,940 cGy given in 33 fractions to partial brain fields that encompassed the primary tumor with a 3 to 4 cm margin. Radiosurgery, used as a technique for boosting the dose to any residual contrast-enhancing mass lesion, was given 2 to 4 weeks after the completion of conventional radiotherapy. Minimum radiosurgical doses ranged from 1,000 to 2,000 cGy (median, 1,200 cGy), whereas maximum doses ranged from 1,250 to 2,500 cGy (median, 1,500 cGy). The median tumor volume at the time of radiosurgery was 4.8 cm3 (range, 1.2 to 72 cm3). Adjuvant chemotherapy was not given. RESULTS: After a median follow-up of 19 months, only nine of 37 (24%) patients have died. Six patients (all glioblastoma multiforme) died of recurrent tumor, whereas death was attributable to complications of treatment in two cases and intercurrent disease in one case. Four patients with recurrent tumor failed at the margins of the radiosurgical treatment volume, whereas two patients progressed locally. One patient is alive with local and marginal failure. Seven (19%) patients underwent reoperation at a median time of 5 months (range, 1 to 14 months) after radiosurgery. CONCLUSION: We conclude that radiosurgery is a useful adjunct to other modalities in the initial management of patients with small, radiographically well-defined malignant gliomas.

Intensity modulated proton therapy.

Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed "pencil beams" of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak-the characteristic peak of dose at the end of range-combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose "painting" within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the highest level of accuracy and pioneered volumetric treatment planning and imaging at a level of quality now standard in X-ray therapy. IMPT requires not only the highest precision tools but also the highest level of system integration of the services required to deliver high-precision radiotherapy.

Detection of HIV antibodies in saliva as a tool for epidemiological studies.

OBJECTIVE: To evaluate the use of saliva specimens for the detection of HIV antibodies among high-risk groups in epidemiological studies. DESIGN: Testing of saliva specimens collected by different methods from individuals with known HIV status. The most reliable method was examined for its usefulness in a field study among a high-risk group. METHODS: Saliva samples were obtained either by using a cotton-wool roll ('Salivette') or as 'whole saliva'. HIV antibodies were determined using commercial enzyme-linked immunosorbent assays (ELISA). Confirmation was performed using a line immunoassay or an immunoblot assay. RESULTS: In 'Salivette' samples, HIV antibodies were detected by ELISA in seven out of 22 seropositive individuals. In contrast, testing of 'whole saliva' samples from 79 HIV-seropositive and 115 HIV-seronegative individuals resulted in a 100% correlation with HIV serum status. The positive reaction of 20 'whole saliva' specimens was confirmed in a line immunoassay, whereas in an immunoblot assay only seven specimens were positive, one negative, and 12 indeterminate. In an HIV prevalence study among drug users, 395 'whole saliva' samples were tested in two different ELISA. Both assays showed complete agreement in detecting 58 positive and 337 negative samples. All positive samples were confirmed by the line immunoassay. CONCLUSION: Our study demonstrates that 'whole saliva' specimens are a good alternative to blood samples in epidemiological studies of HIV prevalence in high-risk groups.

Quadtrees as a representation for irregularly shaped fields in radiotherapy applications.

The choice of data representations in treatment planning software impacts on the accuracy of the treatment plan and the total computation time. We present the quadtree data structure as one such representation for irregularly shaped fields in a three-dimensional electron pencil-beam algorithm. The quadtree subdivides the irregular field into pencil-beams of unequal size and considerably reduces the number of pencil-beams needed in the dose calculation while preserving the calculational accuracy. Small pencil-beams are concentrated around the field edges to provide optimal resolution and computational accuracy in penumbra regions. The quadtree simplifies the evaluation of the pencil-beam fluence at a given depth, and removes systematic errors present in alternative implementations. The quadtree algorithm results in a ten-fold performance improvement when compared to alternative implementations for the irregular field.

The verification of an inverse problem in radiation therapy.

The inverse problem in radiation therapy presents a solution for a fluence distribution based on the specification of a region of dose in a patient. We show results for one such solution based on the inversion of an integral over a function of the fluence profile of a rotating beam. We use Monte Carlo methods and numerical integrations to evaluate dose distributions obtained with the inverse method and show the limitations of this theoretical approach. Our results show that dose to a single circular region at an arbitrary position in a 2-dimensional volume can be calculated. Uniform dose to arbitrarily shaped regions cannot be calculated with this formalism, although practical solutions can still be obtained.

Optimized beam planning for linear accelerator-based stereotactic radiosurgery.

PURPOSE: Current treatment planning for linear accelerator-based stereotactic radiosurgery and radiotherapy is a lengthy and iterative procedure. The planner has to manually select the beam arcs and carefully consider many different selections to ensure target volume coverage while sparing dose to critical organs. In this article we report an optimization procedure that can automatically select the beam arcs based on geometric and dosimetric analysis of the treatment parameters. METHODS AND MATERIALS: The optimization problem is introduced by using a Beam's Eye View (BEV) map where a pattern of lines represents a beam arc combination for a treatment plan. The collection of all possible treatment plans is described by using the concept of phase space where each point corresponds to a particular configuration of the system under consideration, and in this case, a particular beam arc combination. A geometric reduction of the phase space is performed by excluding static beam ports that irradiate too much critical organs and too little target volume. The phase space is further reduced by excluding beam arc combinations that do not comply with treatment convenience considerations and established planning experiences. These reductions significantly reduces the number of beam arc combinations to be considered and thus dramatically simplifies the computational complexity. The method of simulated annealing is then used to the reduced phase space to select the set of beam arcs that provides the best surface dose distribution for the target volume. The optimization procedure is applied to a radiosurgery case to compare the optimized beam arcs with the previously manually planned beam arcs. The procedure is also applied to 10 randomly selected cases for a comparison in terms of tissue-volume ratio calculations. RESULTS: The system is a highly automated beam arc planning tool for stereotactic radiosurgery and stereotactic radiotherapy. Its interactive nature allows the planner to rapidly consider many treatment plans to search for the best option. For the case presented, it is shown that the optimized beams substantially reduce the dose to the postrema. The tissue-volume ratio calculations demonstrate that the optimization often produces clinically superior treatment plans than the manual beam planning method. CONCLUSIONS: Our method of phase space reduction proves to be very useful in approaching the complex problem of treatment planning optimization. Not only does it substantially reduce the number of beam arcs that need to be considered, but it also simplifies the evaluation of the beam arc options. Both of these greatly reduce the computational complexity of the optimization and make the procedure fast and efficient. Moreover, the reduction of phase space adds another layer of interaction between the user and the beam selection procedure, so that the optimization process is well controlled and thus very effective.

A numerical simulation of organ motion and daily setup uncertainties: implications for radiation therapy.

PURPOSE: In radiotherapy planning, the clinical target volume (CTV) is typically enlarged to create a planning target volume (PTV) that accounts for uncertainties due to internal organ and patient motion as well as setup error. Margin size clearly determines the volume of normal tissue irradiated, yet in practice it is often given a set value in accordance with a clinical precedent from which variations are rare. The (CTV/PTV) formalism does not account for critical structure dose. We present a numerical simulation to assess (CTV) coverage and critical organ dose as a function of treatment margins in the presence of organ motion and physical setup errors. An application of the model to the treatment of prostate cancer is presented, but the method is applicable to any site where normal tissue tolerance is a dose-limiting factor. METHODS AND MATERIALS: A Monte Carlo approach was used to simulate the cumulative effect of variation in overall tumor position, for individual treatment fractions, relative to a fixed distribution of dose. Distributions of potential dose-volume histograms (DVHs), for both tumor and normal tissues, are determined that fully quantify the stochastic nature of radiotherapy delivery. We introduce the concept of Probability of Prescription Dose (PoPD) isosurfaces as a tool for treatment plan optimization. Outcomes resulting from current treatment planning methods are compared with proposed techniques for treatment optimization. The standard planning technique of relatively large uniform margins applied to the CTV, in the beam's eye view (BEV), was compared with three other treatment strategies: (a) reduced uniform margins, (b) nonuniform margins adjusted to maximize normal tissue sparing, and (c) a reduced margin plan in which nonuniform fluence profiles were introduced to compensate for potential areas of reduced dose. RESULTS: Results based on 100 simulated full course treatments indicate that a 10 mm CTV to PTV margin, combined with an additional 5 mm dosimetric margin, provides adequate CTV coverage in the presence of known treatment uncertainties. Nonuniform margins can be employed to reduce dose delivered to normal tissues while preserving CTV coverage. Nonuniform fluence profiles can also be used to further reduce dose delivered to normal tissues, though this strategy does result in higher dose levels delivered to a small volume of the CTV and normal tissues. CONCLUSIONS: Monte Carlo-based treatment simulation is an effective means of assessing the impact of organ motion and daily setup error on dose delivery via external beam radiation therapy. Probability of Prescription Dose (PoPD) isosurfaces are a useful tool for the determination of nonuniform beam margins that reduce dose delivered to critical organs while preserving CTV dose coverage. Nonuniform fluence profiles can further alter critical organ dose with potential therapeutic benefits. Clinical consequences of this latter approach can only be assessed via clinical trials.

Variables associated with the development of complications from radiosurgery of intracranial tumors.

Between 5/21/86 and 11/1/89, we treated 64 recurrent or inoperable intracranial tumors in 60 patients (40 primary, 24 metastatic) with stereotactic radiosurgery using a modified 6 MeV linear accelerator at the Joint Center for Radiation Therapy. Patients were followed until death or 1/1/90. The median follow-up was 8 months (2-43 months). Fourteen patients experienced complications from 12 hours to 7 months (median 3 months, but only two patients more than 4 months) following radiosurgery. To determine variables related to complication, we calculated integral dose-volume histograms for 61/64 lesions and the surrounding CT-defined normal tissue. We excluded 16 lesions in 15 patients for follow-up less than 4 months (12 patients) or insufficient treatment information (3 patients). The variables for which higher values were associated with significantly more toxicity in a univariate score test were: a) tumor dose inhomogeneity (p less than 0.00001), b) maximum tumor dose (p = 0.00002), c) number of isocenters (p = 0.00002), d) maximum normal tissue dose (p = 0.00005) and e) tumor volume (p = 0.0001). These variables were all highly correlated with tumor dose inhomogeneity (coefficients of rank correlation 0.75-0.81). Tumor dose inhomogeneity had a much higher loglikelihood in a logistic model than any other single variable and a higher loglikelihood than any other two variables combined. None of the 21 patients with metastatic lesions experienced a complication. When we excluded the metastatic lesions, the above five variables remained significant in univariate tests. The mean tumor dose, number of treatment arcs, total degrees of arc, tumor location, previous radiotherapy, tumor geometry, pretreatment performance status, collimator size, and age were not significantly associated with toxicity. We conclude that radiosurgery of intracranial tumors is associated with a low risk of complications for lesions less than 10cc treated with a single isocenter to maximum tumor doses less than 25 Gy with tumor dose inhomogeneity less than 10 Gy, but that treatment of larger lesions will require new treatment strategies which reduce the tumor dose inhomogeneity associated with multiple isocenter treatments.

Dynamic field shaping for stereotactic radiosurgery: a modeling study.

PURPOSE: This work assesses the relative field shaping advantages of dynamic field shaping devices for stereotactic radiosurgery using a linear accelerator. METHODS AND MATERIALS: We selected 43 intracranial tumors (2.0-4.2 cm maximum dimension, 1.5-25.5 cc tumor volume) out of the first 64 intracranial tumors treated with radiosurgery at the Joint Center for Radiation Therapy. We modeled five field shaping devices, each including a fixed auxiliary circular collimator: (a) fixed circular collimator alone; (b) two independent parallel jaws; (c) four independent rectangular jaws; (d) four independent rotatable jaws; and (e) "ideal" multileaf collimator. We adjusted the model parameters until the minimum target isodose was 80% of the dose delivered to isocenter. We defined the treatment volume ratio as the target volume divided by the treatment volume (volume receiving at least the minimum target dose). We used the treatment volume ratio to compare the five models and the actual patient treatments. RESULTS: For 34 tumors originally treated with one isocenter, the median Treatment Volume Ratio was higher for all of the device models except the fixed circular collimator compared to the actual patient treatments. For the nine tumors originally treated with multiple isocenters, the median Treatment Volume Ratio for the actual multiple isocenter treatments was similar to that for two parallel jaws, four rectangular jaws and four rotatable jaws. Only the median "ideal" collimator treatment volume ratio was higher for these nine tumors. CONCLUSION: Simple field shaping devices have approximately 50% of the conformal advantage of an "ideal" multileaf collimator. Approximately 50% of typical radiosurgical tumors between 2 and 4 cm have field shaping advantages which exceed the geometrical uncertainties inherent in linear accelerator radiosurgery treatments. The three models, two parallel, four rectangular, or four rotatable independent jaws would improve current linear accelerator technology by providing homogeneous doses with equivalent field shaping for most tumors originally treated with inhomogeneous multiple isocenter plans (6/9 tumors in the current series).

A clinical method for real-time dosimetric guidance of transperineal 125I prostate implants using interventional magnetic resonance imaging.

PURPOSE: The clinical utility of an interventional magnetic resonance (IMR)-guided implant technique with real-time dosimetric feedback is presented. METHODS AND MATERIALS: The work was carried out at a IMR unit at Brigham and Women's Hospital. Planning and dosimetric feedback were provided by a software system that provides an interface to the IMR images, anatomy demarcation, template registration, dose calculation engine for planning, and evaluating the implant. Planning during the procedure permits the incorporation of actual needle trajectories in the dose calculations. RESULTS: Fifteen patients were planned in the treatment position. During source placement, actual needle locations were incorporated into the dose calculations. After accounting for the observed needle trajectories of the planned needles, 14 of 15 patients (93%) required additional sources to achieve the desired coverage of the target volume. CONCLUSION: A brachytherapy implant procedure which provides clinically significant advances has been implemented. Specifically, the planning system allows dosimetric validation of the needle placement. This procedure is effective in delivering brachytherapy to the target volume and assuring that the implant is delivered in accordance with the preplan. The dosimetric feedback could be incorporated in ultrasound-guided implants.

Comparison of miniature multileaf collimation (MMLC) with circular collimation for stereotactic treatment.

PURPOSE: A prototype Miniature Multi-Leaf Collimator (MMLC) designed specifically for radiosurgery and small field radiotherapy has been fabricated and evaluated at the University of Texas M. D. Anderson Cancer Center (UTMDACC). This work demonstrates the advantages of a computer-controlled MMLC vs. conventional circular collimation for the treatment of an irregularly shaped target volume in the brain. METHODS AND MATERIALS: Two patient treatments were selected for this comparison from 38 intracranial tumors treated with radiosurgery at UTMDACC from 8/6/91 to 5/10/94. Target contours and critical structures defined for one of the patients was used to create a simulated target volume and critical structures in a spherical head phantom. Computer simulations were performed using traditional single isocenter treatment with a circular collimator for a set of six arcs. The same arc paths were used to compute the dose distribution for the MMLC and conformed beam geometries were defined using a three-dimensional (3D) treatment planning system with beam's eye view capabilities. Then, the calculated dose distribution for a single isocenter, conformal treatment was delivered to the spherical head phantom under static conditions by shaping the MMLC to conform the target volume shape projected as a function of couch rotation and gantry angle. Planar dose distributions through the target volume were measured using therapy verification film located in the phantom. The measurements were used to verify that the 3D treatment planning system was capable of simulating the MMLC technique. For the second patient with a peanut-shaped tumor, the 3D treatment planning calculations were used to compare dose distributions for the MMLC and for traditional single and multiple isocenter treatments using circular collimators. The resulting integral dose-volume histograms (DVHs) for the target volume, normal brain, and critical structures for the three treatment techniques were compared. RESULTS: (a) Analysis of the film dosimetry data exemplified the degree of conformation of the high-dose region to the target shape that is possible with a computer-controlled MMLC. (b) Comparison of measured and calculated dose distributions indicates that the 3D treatment planning system can simulate the MMLC treatment. (c) Comparison of DVHs from the single isocenter MMLC and circular collimator treatments shows similar coverage of the target volume with increased dose to the brain for circular collimation (4). Comparison of DVHs from the single isocenter MMLC with the multiple isocenter circular collimator treatment approach shows a more inhomogeneous dose distribution through the target volume and increased dose to the brain for the latter. CONCLUSION: Dosimetry data for single isocenter treatments using computer-controlled field shaping with a MMLC demonstrate the ability to conform the dose distribution to an irregularly shaped target volume. DVHs validated that the single isocenter MMLC treatment is preferable to both single and multiple isocenter, circular collimator treatment because it provides a more uniform dose distribution to an irregularly shaped target volume and reduces the dose to surrounding brain tissue for the example cases.