Clinical Outcomes of Proton Radiotherapy for Uveal Melanoma.

AIMS: Although clinical experience with proton beam radiotherapy (PBT) for most tumours is limited, there is relatively longstanding experience for uveal melanomas. Because of potential to reduce ocular toxicities, PBT is an attractive option for these tumours. However, summative data remain scarce. We systematically reviewed clinical outcomes of uveal melanoma patients treated with PBT, to comprehensively assess outcomes such as tumour control, survival, enucleation rates, toxicity and visual acuity preservation. MATERIALS AND METHODS: A systematic search of PubMed, EMBASE, abstracts from meetings of the American Societies for Radiation Oncology and Clinical Oncology, and the Particle Therapy Co-Operative Group was conducted from 2000 to 2015. Fourteen original investigations from 10 different institutions were analysed. RESULTS: Most tumours were choroidal and medium-/large-sized, and received 50-70 Cobalt Gray equivalent dose; more recent data reported lower doses. Five year local control rates exceed 90%, which persisted at 10 and 15 years. Five-year overall survival rates ranged from 70 to 85%, 5 year metastasis-free survival and disease-specific survival rates from 75 to 90%, with more recent series reporting higher values. With the removal of smaller studies, 5 year enucleation rates were consistently between 7 and 10%. Many patients (60-70%) showed a post-PBT visual acuity decrease, but still retained purposeful vision (>20/200); more recent, higher-volume series reported superior numbers. Complication rates were quite variable but showed improvements on historical plaque brachytherapy data. Only one randomised trial directly compared particle therapy (helium) with plaque brachytherapy, showing the former to be superior; this is addressed separately. CONCLUSIONS: PBT is an excellent modality to treat uveal melanomas, with high survival outcomes and visual acuity preservation. Although there are low toxicity and enucleation rates, the recent development of supportive therapies for radiation toxicities can further decrease clinical adverse effects.

On the use of hyperpolarized helium MRI for conformal avoidance lung radiotherapy.

We wanted to illustrate the feasibility of using hyperpolarized helium magnetic resonance imaging (HPH-MRI) to obtain functional information that may assist in improving conformal avoidance of ventilating lung tissue during thoracic radiotherapy. HPH-MRI images were obtained from a volunteer patient and were first fused with a proton density-weighted (PD(w)) MRI to provide corresponding anatomic detail; they were then fused with the treatment planning computed tomography scan of a patient from our treatment planning database who possessed equivalent thoracic dimensions. An optimized treatment plan was then generated using the TomoTherapy treatment planning system, designating the HPH-enhancing regions as ventilation volume (VV). A dose-volume histogram compares the dosimetry of the lungs as a paired organ, the VV, and the lungs minus the VV. The clinical consequences of these changes was estimated using a bio-effect model, the parallel architecture model, or the local damage (f(dam)) model. Model parameters were chosen from published studies linking the incidence of grade 3+ pneumonitis, with the dose and volume irradiated. For two hypothetical treatment plans of 60 Gy in 30 fractions delivered to a right upper-lobe lung mass, one using and one ignoring the VV as an avoidance structure, the mean normalized total dose (NTD(mean)) values for the lung subvolumes were: lungs = 12.5 Gy3 vs. 13.52 Gy3, VV = 9.94 Gy3 vs. 13.95 Gy3, and lungs minus VV = 16.69 Gy3 vs. 19.16 Gy3. Using the f(dam) values generated from these plans, one would predict a reduction of the incidence of grade 3+ radiation pneumonitis from 12%-4% when compared with a conventionally optimized plan. The use of HPH-MRI to identify ventilated lung subvolumes is feasible and has the potential to be incorporated into conformal avoidance treatment planning paradigms. A prospective clinical study evaluating this imaging technique is being developed.

Combined radio- and chemotherapy of brain tumours in adult patients.

In order to examine the current standards of care regarding combined radio- and chemotherapy for adult patients with brain tumours, a review was carried out of recent studies examining surgery, radiotherapy and chemotherapy in high-grade glioma, medulloblastoma and primary central nervous system lymphoma. The integration of the oral cytotoxic agent temozolomide into current treatment protocols of postoperative combination therapy with radiation and drugs in high-grade glioma is discussed. In glioblastoma, the landmark phase III trial by the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada has defined the current standard of care. Attempts to optimise the schedule of temozolomide administration and to combine this regimen with additional agents are currently ongoing. Additional trials are examining whether temozolomide-radiotherapy combination regimens should also be the standard of care in patients with anaplastic glioma. The role of postsurgery procarbazine, lomustine, and vincristine (PCV) in addition to radiotherapy in anaplastic glioma with oligodendroglial features is controversial, as two randomised trials failed to show improved survival, despite longer progression-free survival. In medulloblastoma, no comparable landmark trial exists and therefore combined radiochemotherapy must be considered investigational. In primary central nervous system lymphoma, high-dose methotrexate-based chemotherapy is the cornerstone of therapy and the value of consolidation radiotherapy for patients achieving a complete response is controversial, even in younger patients who have a lower risk of neurotoxicity than older patients. The challenges associated with brain tumour treatment remain formidable, but rationally designed clinical trials are gradually leading to improved outcomes.

Dose escalated, hypofractionated radiotherapy using helical tomotherapy for inoperable non-small cell lung cancer: preliminary results of a risk-stratified phase I dose escalation study.

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to < or = 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTD(mean) (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% +/- 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.

The impact of linac output variations on dose distributions in helical tomotherapy.

It has been suggested for quality assurance purposes that linac output variations for helical tomotherapy (HT) be within +/-2% of the long-term average. Due to cancellation of systematic uncertainty and averaging of random uncertainty over multiple beam directions, relative uncertainties in the dose distribution can be significantly lower than those in linac output. The sensitivity of four HT cases with respect to linac output uncertainties was assessed by scaling both modeled and measured systematic and random linac output uncertainties until a dose uncertainty acceptance criterion failed. The dose uncertainty acceptance criterion required the delivered dose to have at least a 95% chance of being within 2% of the planned dose in all of the voxels in the treatment volume. For a random linac output uncertainty of 5% of the long-term mean, the maximum acceptable amplitude of the modeled, sinusoidal, systematic component of the linac output uncertainty for the four cases was 1.8%. Although the measured linac output variations represented values that were outside of the +/-2% tolerance, the acceptance criterion did not fail for any of the four cases until the measured linac output variations were scaled by a factor of almost three. Thus, the +/-2% tolerance in linac output variations for HT is a more conservative tolerance than necessary.

Multiple hyperbaric oxygenation (HBO) expands the therapeutic window in acute spinal cord injury in rats.

Hyperbaric oxygenation (HBO) therapy has been reported to improve neurological recovery following spinal cord injury (SCI). In the present study, we examined whether multiple HBO expands the therapeutic window for acute SCI. Single HBO (2.8 ATA, 1 hour) treatment was used at 30 minutes, 3 hours, and 6 hours following SCI, and serial HBO treatment (once daily for 1 week) at 6 hours and 24 hours post-injury. Mild SCI was induced by adjusting the height for a weight drop insult (10 g) to 6.25 mm above the exposed spinal cord. The group of animals receiving a single HBO intervention beginning at 30 minutes and 3 hours, or serial HBO treatment starting at 6 hours following the injury had a significantly better neurological recovery than animals with SCI only. The results of this study demonstrate that multiple HBO expands the therapeutic window for acute SCI to 6 hours after injury, further that serial HBO administration is superior to single HBO therapy.

Pineal sarcoma.

We report a case of fibrosarcoma arising in the pineal of a 36-year-old female patient. She died at the age 43 following biopsy, radiation therapy, tumor resection, chemotherapy, and stereotactic radiosurgery. Light microscopic study of all tissues obtained, including immunohistochemistry and electron microscopy of surgically resected tumor and autopsied tissue revealed a slowly progressing primary fibrosarcoma.

Assessment of patient-independent intrinsic error for a noninvasive frame for fractionated stereotactic radiotherapy.

The purpose of our study was to examine the extent of patient-independent intrinsic error associated with multiple, repeat remounting of the Laitinen Stereoadapter. The Laitinen frame was repeatedly mounted on a solid water phantom and imaged using computed tomography (CT). The phantom contained five targets located in the center, anterior, right, left, and posterior orientations. The images were processed, fused, and analyzed on the Pinnacle 3-D treatment planning system. The coordinate values (in the x, y, and z directions) for each target were determined for each mounting, and an absolute mean deviation was calculated for 11 repetitions. The mean deviation in the x, y, and z direction for the central and right target, and in the x and y direction for the posterior and anterior target was less than 2.0 mm. However, the mean error in the z direction of the anterior and posterior targets was 1.79 +/- 1.02 mm and 2.20 +/- 1.32 mm, respectively. Rotational misalignment during repeat frame fixation contributed to the observed deviations and in particular affected the antero-posterior plane. With the exception of two occasions where an obvious mounting error occurred, a significant portion of error from remounting the Laitinen Stereoadapter is associated with the operator and the imaging process. The observation of an angular displacement around the axis through the earplugs suggests that a certain degree of rotational misalignment in daily remounting is possible. Targets in the antero-posterior plane are most susceptible to localization error as a consequence of rotational misalignment. In summary, the overall error is within the limits of current imaging technology but not within submillimeter accuracy. Clinical application should take these errors into consideration when designing field margins.

Late recurrence of a primitive neuro-ectodermal tumor.

Late recurrences after therapy are rare in primitive neuro-ectodermal tumor (PNET). Most recurrences occur within the first 2 years after therapy, although a small number of recurrences may occur up to 5 years after therapy. We present a rare case of a recurrence of PNET in a 31-year-old woman 17 years after her initial presentation. The potential biological implications of this late recurrence as well as responses to subsequent therapy, including temozolomide, are discussed.

Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Quality of life assessment in advanced non-small-cell lung cancer patients undergoing an accelerated radiotherapy regimen: report of ECOG study 4593. Eastern Cooperative Oncology Group.

PURPOSE: To prospectively evaluate the quality of life (QOL) before, at completion, and after therapy for patients receiving an accelerated fractionation schedule of radiotherapy for advanced, unresectable non-small-cell lung cancer in a Phase II multi-institutional trial. METHODS AND MATERIALS: The Functional Assessment of Cancer Therapy-Lung (FACT-L) patient questionnaire was used to score the QOL in patients enrolled in the Eastern Cooperative Oncology Group Phase II trial (ECOG 4593) of hyperfractionated accelerated radiotherapy in non-small-cell lung cancer. Radiotherapy (total dose 57.6 Gy in 36 fractions) was delivered during 15 days, with three radiation fractions given each treatment day. The protocol was activated in 1993, and 30 patients had accrued by November 1995. The FACT-L questionnaire was administered at study entry (baseline), on the last day of radiotherapy (assessment 2), and 4 weeks after therapy (assessment 3). The FACT-L includes scores for physical, functional, emotional, and social well-being (33 items), and a subscale of lung cancer symptoms (10 additional items). The summation of the physical, functional, and lung cancer symptom subscales (21 items) constitutes the Trial Outcome Index (TOI), considered the most clinically relevant outcome measure in lung cancer treatment trials. RESULTS: The FACT-L completion rates at the designated study time points were as follows: baseline, 30 of 30 (100%); assessment 2, 29 (97%) of 30; and assessment 3, 24 (80%) of 30. At treatment completion, statistically significant declines in QOL scores were noted, compared with baseline for physical and functional well-being. Emotional well-being scores improved at both assessment 2 and assessment 3. The physical and functional scores returned approximately to baseline values at assessment 3. The change in TOI score was evaluated as a function of the clinical response to treatment, toxicity grade, and survival; no clear association was noted. A trend for the largest decrease in QOL was noted for patient groups with shorter survival times. The mean change in the TOI score from baseline to assessment 3 was -8.96 for patients surviving < 52 weeks vs. -0.95 for those surviving > 52 weeks. CONCLUSIONS: The FACT-L questionnaire can be successfully administered to non-small-cell lung cancer patients enrolled in a prospective Phase II trial of accelerated radiation fractionation. The decrement in physical and functional QOL during treatment returned to baseline level at 4 weeks after treatment. Emotional well-being improved at all time points. A trend was noted for shorter survival times in patients with the largest negative change in TOI score. These data suggest that the clinical use of hyperfractionated accelerated radiotherapy did not cause a significant, long-term decrease in the QOL of the treated patients, and that it is feasible to perform a QOL study of patients enrolled in such a trial.

Gadolinium in human glioblastoma cells for gadolinium neutron capture therapy.

157Gd is a potential agent for neutron capture cancer therapy (GdNCT). We directly observed the microdistribution of Gd in cultured human glioblastoma cells exposed to Gd-diethylenetriaminepentaacetic acid (Gd-DTPA). We demonstrated, with three independent techniques, that Gd-DTPA penetrates the plasma membrane, and we observed no deleterious effect on cell survival. A systematic microchemical analysis revealed a higher Gd accumulation in cell nuclei compared with cytoplasm. This is significant for prospective GdNCT because the proximity of Gd to DNA increases the cell-killing potential of the short-range, high-energy electrons emitted during the neutron capture reaction. We also exposed Gd-containing cells to thermal neutrons and demonstrated the GdNC reaction effectiveness in inducing cell death. These results in vitro stimulated in vivo Gd-DTPA uptake studies, currently underway, in human glioblastoma patients.

Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases.

PURPOSE: Motexafin gadolinium is a magnetic resonance imaging (MRI)--detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase Ib/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. PATIENTS AND METHODS: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase Ib, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. RESULTS: In phase Ib, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium's tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. CONCLUSION: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.

Multiple daily fractionation radiotherapy schedules in lung cancer.

Lung cancer is the number one worldwide cancer killer, and in spite of therapeutic advances, the overall impact on survival has remained very modest. For both small and non-small-cell lung cancer, treatment trends have shifted toward combined-modality approaches, chemotherapy for the control of systemic micrometastases, and radiotherapy for intrathoracic control. However, on both counts, rates of failure remain unacceptably high, and several novel strategies are currently being explored. The use of altered fractionation, including multiple daily fractions, reflects one approach for modifying radiotherapy. The two most common approaches are hyperfractionation and acceleration, the former designed to reduce late normal tissue toxicities and the latter to counteract accelerated tumor repopulation. Recent randomized trials suggest that such approaches may result not only in lowered rates of intrathoracic failure but also in improved survival.

Radiotherapy for brain tumors.

Over the last 2 years, several advances have been made in the field of radiotherapy for brain tumors. Key advances are summarized in this review. Crucial technologic advances, such as radiosurgery, fractionated stereotactic radiotherapy, and intensity-modulated radiotherapy, are discussed. Better understanding of the interaction between the processes of angiogenesis, apoptosis, cell-cycle regulation, and signal transduction and the effects of ionizing radiation has made it clear that many of these "new agents" are, in fact, valuable modulators of the radiation response. Another exciting molecular discovery is the recognition of radiation-induced promoters that can be exploited to cause spatially and temporally configured expression of selected genes; this approach may represent the ideal application of conformal radiation techniques in the future, yielding well-defined genetic changes in specifically targeted tissues. The final "frontier" covered in this review is the newer categories of radiosensitizers, ranging from topoisomerase-I inhibitors, to expanded metalloporphyrins, to oxygen- dissociating agents.

The contemporary role of radiation therapy in the management of lung cancer.

This article reviews the current role of radiotherapy in the management of non-small-cell lung cancer. This modality is used extensively in lung cancer patients. In a variety of different contexts, the specific indications, results, controversies, and emerging areas are highlighted, with an emphasis on the author's personal techniques and a review of the pertinent literature.

Pilot and safety trial of carboplatin, paclitaxel, and thalidomide in advanced non small-cell lung cancer.

We performed a pilot study to assess the safety of thalidomide in combination with standard chemo-therapy in patients with advanced non small-cell lung cancer. Patients with unresectable stage IIIA, IIIB, or IV disease were enrolled starting in July 1999. Patients received paclitaxel 225 mg/m2 over 3 hours and carboplatin area under the curve = 6.0 with thalidomide at a starting daily dose of 200 mg. The thalidomide dose was escalated, if tolerated, by 200 mg per week to a target dose of 1000 mg per day and could continue for up to 6 months. Patients with stages IIIA and IIIB disease without effusion received radiotherapy with concurrent thalidomide after 2 cycles of chemotherapy. Nine patients were enrolled: one with IIIA disease, three with IIIB disease, and five with stage IV disease. Five of nine patients had previously been treated with chemotherapy and/or radiotherapy. The most frequent side effects noted were fatigue, myalgia, constipation, neuropathy, and myelosuppression. Sixteen of the 17 (94%) episodes of grade 3 or 4 hematologic toxicity occurred in the five patients who had previously received chemotherapy, although no patients developed neutropenic fever. The median tolerated daily thalidomide dose was 600 mg. One patient with IIIA disease had a partial response after 2 cycles of chemotherapy and went on to receive radiotherapy with thalidomide. One patient with stage IV disease continues on this study with stable disease at 187 days. The median time to progression was 118 days. This preliminary data supports the further investigation of this combination in chemotherapy-naive patients with advanced non small-cell lung cancer.

A phase I trial of 1,3-bis(2-chloroethyl)-1-nitrosourea plus temozolomide: a North American Brain Tumor Consortium study.

The North American Brain Tumor Consortium conducted a phase I trial of the combination 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide. Eligibility included a patient with a cancer type that was considered refractory to standard therapy. Prior nitrosourea treatments were not permitted. There were parallel dose escalations in two treatment schedules. Forty-five patients were enrolled during an 18-month period. The maximum tolerated doses (MTDs) when temozolomide followed BCNU (Arm A) were temozolomide at 550 mg/m2/p.o. and BCNU at 150 mg/m2/i.v.), whereas the MTD when temozolomide preceded BCNU (Arm B) was temozolomide at 400 mg/m2/p.o. and BCNU at 100 mg/m2/i.v. Toxicity was predominantly hematologic, although there were three instances of pulmonary toxicity, which in one case could have represented potentiation of nitrosourea-induced pulmonary fibrosis. The half-life of temozolomide was 1.86 (+/-0.31) h. There was a moderate relationship between dose and peak concentration and a strong relationship between dose and plasma concentration time curve. Pharmacokinetic parameters of temozolomide were unaffected by the treatment schedule, so the difference in MTD between the schedules is likely due to a biologic rather than a pharmacokinetic sequence interaction. There were 9 partial responses among 43 patients evaluable for response, including 5 of 25 with a histologic diagnosis of glioblastoma. The recommended dose and schedule for phase II trials of this regimen are BCNU 150 mg/m2/i.v. followed in 2 h by temozolomide 550 mg/m2/p.o. repeated every 6 weeks. We are also recommending screening and periodic pulmonary function testing during treatment to assess the possible potentiation of nitrosourea-induced pulmonary fibrosis.

Development of a unique phantom to assess the geometric accuracy of magnetic resonance imaging for stereotactic localization.

OBJECTIVE: To test the spatial accuracy of coordinates generated from magnetic resonance imaging (MRI) scans, using the Brown-Roberts-Wells head frame and localizer system (Radionics, Inc., Burlington, MA). METHODS: An anthropomorphic head phantom, consisting of a two-dimensional lattice of acrylic spheres (4-mm diameter) spaced 10 mm apart and embedded in a brain tissue-mimicking gelatin-agar gel, was constructed. The intersphere distances for the target lattice positions in MRI and computed tomographic scan sets were compared. The data sets were fused, and differences in fiducial marker and intraphantom target positions were measured. RESULTS: Intersphere distances were identical for the MRI and computed tomographic scan sets (10 +/- 0.1 mm). Differences in fiducial marker positions [maximal lateral difference, 0.97 mm; mean absolute lateral difference, 0.69 +/- 0.22 mm; maximal anteroposterior (AP) difference, 1.99 mm; mean absolute AP difference, 1.29 +/- 0.67 mm] were correlated with differences in intraphantom target positions (maximal lateral difference, 0.83 mm; mean absolute lateral difference, 0.28 +/- 0.24 mm; maximal AP difference, -1.97 mm; mean absolute AP difference, 1.63 +/- 25 mm; maximal vertical difference, -0.73 mm; mean absolute vertical difference, 0.34 +/- 0.21 mm). This suggested that improper fiducial rod identification and the subsequent transformation to stereotactic coordinate space were the greatest sources of spatial uncertainty. CONCLUSION: With computed tomographic data as the standard, these differences resulted in maximal and minimal composite uncertainties of 2.06 and 1.17 mm, respectively. The measured uncertainties exceed recommended standards for radiosurgery but allow the possible use of MRI-based stereotactic treatment planning for certain intracranial lesions, if the errors are corrected using appropriate software. Clinicians must recognize that error magnitudes vary for different systems, and they should perform systematic, scheduled, institutional error analyses as part of their ongoing quality assurance processes. This phantom provides one tool for measuring such variances.