Initial validation and clinical experience with 3D optical-surface-guided whole breast irradiation of breast cancer.

We had introduced 3D optical surface-guided radiotherapy (SGRT) of the breast cancer (BC). We then initiated the feasibility, accuracy, and precision studies of stereovision in detection of any breast displacement through the course of treatment for total thirty breasts undertaken whole breast irradiation (WBI). In the SGRT, CT-based plan data were parsed into an in-house computer program through which the reference surfaces were generated in 3D video format. When patients were positioned on treatment Tables, real-time stereovisions were rapidly acquired while the live surface tracking shown steady thorax motion. The real-time surface images were automatically aligned with the reference surface and detected shape and location changes of the breast were online corrected through the Table and beam adjustments. Accumulated dose to each patient was computed according to the frequency distribution of the measured breast locations during beam on time. Application of SGRT had diminished large skin-marking errors of > 5-mm and daily breast-setup errors of >10-mm that occurred on half of cases. Accuracy (mean) and precision (two standard deviations) of the breast displacements across the tangential field edges in the (U, V) directions were improved from (-0.5 ± 8.8, 2.2 ± 10.8) mm in conventional setup to (0.4 ± 4.6, 0.7 ± 4.4) mm in the final position while intra-fractional motion contributed only (0.1 ± 2.8, 0.0 ± 2.2) mm in free breathing. Dose uniformity and coverage to targets had both been increased by up to 10% and the lung or heart intersections have been decreased by half of those volumes if they were irradiated at the initial positions. SGRT of BC appears to be feasible regardless of skin tones, as fast as a snapshot for 3D imaging, and very accurate and precise for daily setup of flexible breast targets. Importantly, the technique allows us to verify the breast shape and position during beam-on time.

WE-E-BRB-03: Development of a Deformable Dosimetric Phantom for Verification of 4D Dose Calculation Algorithms.

PURPOSE: To develop a deformable lung phantom to verify voxel mapping and dose accumulation in 4D dose calculation algorithms used under different scenarios of tissue compression. METHODS: The phantom consists primarily of a heterogeneous sponge with an embedded tissue-equivalent tumor. The sponge is wrapped in a latex balloon housed in a Lucite cylinder. The balloon is attached to a piston that compresses the sponge to mimic the human diaphragm. The phantom was programmed to simulate different breathing patterns. Radiochromic films and TLD were embedded in the sponge for 4D dosimetry algorithm verification. 37 anatomical landmarks were manually tracked to verify voxel mappings for four deformable image registration (DIR) algorithms: in-house developed Demons and finite element model algorithms, and two B-Spline based Velocity AI registration algorithms performed between end-inhale and end-exhale. A 6MV photon beam was simulated with BEAMnrc/DOSXYZnrc on the end-inhale image with the dose mapped to the end-exhale using voxel-based linear dose mapping (LDM) and particle-based energy-mass congruence mapping (EMCM) methods. RESULTS: The mean density of the artificial lung was increased by 10.2% as the sponge was compressed by 2.5cm. The reproducibility of the phantom deformation was within image resolution (1×1×3 mm3), and the accuracy of four DIR registrations of the extreme phases was within 3.0mm. With the same registration displacement vector field (DVF), EMCM and LDM had different doses mapped to the end- exhale image. Their difference at the center of a beam was up to 8.3% for a Demons DVF and 5.8% for a Velocity DVF. The maximum difference between EMCM and LDM was 13.2% at beam penumbra. CONCLUSIONS: The developed deformable dosimetric phantom readily demonstrated variations among different dose addition and image registration algorithms, and is appropriate to serve as a QA tool for verification of 4D dose calculation algorithms. The research was supported by NIH/NCI R01CA140341.

SU-E-T-487: Spatial Assessment of Dose Distributions for Patients with Lung Cancer Treated with Stereotactic Ablative Radiotherapy (SABR).

PURPOSE: We hypothesize that PTV margin dose is an important factor for local tumor control. We evaluated dose distributions for patients originally treated with pencil-beam (PB)-based plans and retrospectively calculated with Monte Carlo (MC) method, with emphasis on the spatial region between the ITV and PTV (PTV-margin), where the largest dose differences were expected. METHODS: Forty-six stage I-II lung cancer patients with 51 lesions treated with SABR were retrospectively analyzed (23 central and 28 peripheral tumors). All patients received 4DCT imaging, and an ITV was generated from the maximum intensity projection and subsequent review of four 4DCT phases. An isotropic 3mm ITV-to-PTV margin was used. The iPlan TPS was used to generate the original treatment plans using PB-based heterogeneity correction. MC doses were recalculated using the same MUs as in the PB plan. Dose distributions for the ITV, PTV-margin, and PTV were analyzed using generalized equivalent uniform dose (gEUD) with a = - 20. Student's paired t-test elucidated differences between PB and MC-based gEUD and the two different tumor locations. RESULTS: Mean ITV and PTV volumes were 24.2 cc (range: 2.2 to 99.3 cc) and 50.4 cc (range: 6.4 to 229.7 cc), respectively. The mean gEUDs of ITV, PTV-margin and PTV, normalized to PB-based 100% isodose were 1.02+/-0.04, 1.01+/-0.04 and 1.01+/-0.04 for PB-based plans, compared to 0.94+/-0.06, 0.88+/-0.08 and 0.90+/-0.08 (all p<0.05) for MC-based plans. The maximum overestimations with the PB algorithm in the PTV-margin average dose were 10.4% and 19.6% (p < 0.05) for peripheral tumor cases and central tumor cases, respectively. CONCLUSIONS: PB-based dose distributions showed the highest dose overestimation (relative to MC) in the PTV-margin spatial region. Analysis of spatial dose differences is an important precursor toward assessment of patterns-of-local failure, to be investigated in future work to explore possible association between dose and regions of failure. Acknowledgement: supported in part by grants from NIH R01 CA106770 and from Varian Medical Systems.

SU-E-J-59: Dual Imaging Guided Localization System for Spine Radiosurgery.

PURPOSE: To compare localization accuracies between an ExacTrac and cone beam computed tomography (CBCT) systems for single fraction spine adiosurgery. The work also aimed to evaluate the inherent systematic deviation of both ExacTrac and CBCT systems to achieve highly accurate localization in the spine radiosurgery. METHODS: ExacTrac and CBCT imaging systems were evaluated using the linac isocenter as the mutual reference point. First, a BB was placed in an anthropomorphic pelvic phantom. The phantom was localized with both imaging systems and the procedure was repeated 12 times. These results were used to devise a localization protocol using both imaging systems in spine radiosurgery, and employed for 51 patients (81 isocenters) prescribed for single fraction treatment. The displacement discrepancy between the isocenter and two systems were quantified in four dimensions (three translations, one rotation). A Student's two-tailed t-test was used to test for significant differences between the two imaging systems. RESULTS: The phantom study showed 1.4±0.5, 0.6±0.5, and 0.1±0.5 mm differences between the two imaging systems in the anterior/posterior (A/P), superior/inferior (S/I) and left/right (L/R) directions, respectively. The angular difference was minimal along all three axes. The patient study revealed similar isocenter discrepancies between ExacTrac and CBCT of 1.1 ± 0.7 mm, 1.0±0.9 mm, and 0.2±0.9 mm in the A/P, S/I, and L/R directions, respectively, with the A/P and S/I directions showing statistical significance ((t(80) = 13.5 and 7.6 respectively, p = 0.000). The couch yaw discrepancy was 0 ± 0.3°. Overall, 1 mm systematic differences were observed in the A/P and S/I directions between ExacTrac and CBCT localization systems, both in phantom and patient. A procedure was developed to mitigate this systematic discrepancy. CONCLUSIONS: These findings have justified our patient localization tolerance levels of 2 mm translation and 1 degree rotation for spine SRS treatment.

SU-E-T-197: A Comprehensive Variance Reporting System and an Analysis of Variances Reported at Our Institution.

PURPOSE: It is essential for radiation oncology departments to have comprehensive patient safety and quality programs. Two years ago we undertook a systematic review of our safety/QA program. Existing policies were updated and new policies created where necessary. One crucial component of any safety/QA program is continually updating it based on current information, the 'check' and 'act' portions of the Deming Cycle. We accomplished this with a transparent variance reporting system and a safety/QA committee reviewing and acting on reported variances. METHODS: With 5 radiation oncology centers in our institution, we needed to devise a system that would allow anyone to report a variance and provide our QA committee the ability to review variances system-wide. We developed the system using web-based tools. The system allows individuals to report variances, anonymously or named, specify the nature of the variance and indicate the tools used to identify the variance. RESULTS: In 2011, 285 variances were reported, 102 were reported by physicists, 86 anonymously, 71 by therapists and 26 by dosimetrists. We realized the need to develop clear classifications for variances. We added a high priority category, defined as variances which resulted in or had the potential to result in harm to a patient or when a policy is purposely overridden. Of the 285 variances reported, 5 were high priority. We created a process variance category, defined as variances where a specific clinical process is not followed. Of the 285 reported variances 155 were process variances. CONCLUSIONS: Reporting of variances through a centralized database is central toward developing a robust patient safety/quality assurance program. Anonymous reporting fosters a non-punitive environment, and promotes the 'safety culture'. The goal of such a system is to review trends in clinical processes and ultimately to improve safety/quality by reducing variances associated with these processes.

Patterns of missing mini mental status exam (MMSE) in radiation therapy oncology group (RTOG) brain cancer trials.

The Mini Mental Status Exam (MMSE) instrument has been commonly used in the Radiation Therapy Oncology Group (RTOG) to assess mental status in brain cancer patients. Evaluating patient factors in relation to patterns of incomplete MMSE assessments can provide insight into predictors of missingness and optimal MMSE collection schedules in brain cancer clinical trials. This study examined eight RTOG brain cancer trials with ten treatment arms and 1,957 eligible patients. Patient data compliance patterns were categorized as: (1) evaluated at all time points (Complete), (2) not evaluated from a given time point or any subsequent time points but evaluated at all the previous time points (Monotone drop-out), (3) not evaluated at any time point (All missing), and (4) all other patterns (Mixed). Patient characteristics and reasons for missingness were summarized and compared among the missing pattern groups. Baseline MMSE scores and change scores after radiation therapy (RT) were compared between these groups, adjusting for differences in other characteristics. There were significant differences in frequency of missing patterns by age, treatment type, education, and Zubrod performance status (ZPS; P < 0.001). Ninety-two percent of patients were evaluated at least once: seven percent of patients were complete pattern, 49% were Monotone pattern, and 36% were mixed pattern. Patients who received RT only regimens were evaluated at a higher rate than patients who received RT + other treatments (49-64% vs. 27-45%). Institutional error and request to not be contacted were the most frequent known reasons for missing data, but most often, reasons for missing MMSE was unspecified. Differences in baseline mean MMSE scores by missing pattern (Complete, Monotone dropout, Mixed) were statistically significant (P < 0.001) but differences were small (<1.5 points) and significance did not persist after adjustment for age, ZPS, and other factors related to missingness. Post-RT change scores did not differ significantly by missing pattern. While baseline and change scores did not differ widely by missing pattern for available measurements, incomplete data was common and of unknown reason, and has potential to substantially bias conclusions. Higher compliance rates may be achievable by addressing institutional compliance with assessment schedules and patient refusal issues, and further exploration of how educational and health status barriers influence compliance with MMSE and other tools used in modern neurocognitive batteries.

Morphologic magnetic resonance imaging features of therapy-induced cerebral necrosis.

To describe the morphologic magnetic resonance imaging (MRI) findings in histologically proven therapy-induced cerebral necrosis. We retrospectively reviewed the morphologic MRI findings in patients with therapy-induced cerebral necrosis. Images were reviewed for size, location, and characteristics of signal intensity abnormalities and T1-contrast enhancement. Images were also assessed for mass effect, necrosis, cyst, atrophy, cortical thinning, and leukoencephalopathy. The individual imaging characteristics were correlated with clinical and treatment variables. There were 44 patients. Seventy percent had a glioma, all patients had received radiation, and 57% had received chemotherapy in close proximity to radiation. All images demonstrated contrast enhancement, predominantly in the white matter. Enhancement was present in the periventricular/subependymal region in 50% of cases and the corpus callosum in 27%. The most common pattern of lesion peripheral enhancement was "spreading wavefront" and of interior enhancement was "Swiss cheese/soap bubble." The enhancing lesion was single in 60% of cases. Mass effect was present in 93% of patients. Location and patterns of enhancement were significantly associated with the interval from brain radiation to the diagnosis of therapy-induced cerebral necrosis, tumor histology, patient age, type of radiation, and administration of systemic chemotherapy. This is the largest study of the morphologic conventional MRI findings in pathologically confirmed therapy-induced cerebral necrosis. We characterized the imaging findings in a variety of tumor types following a variety of radiation treatments and other antineoplastic therapy. These findings may be of value in identifying therapy-induced cerebral necrosis in patients treated for a brain tumor.

A method for repositioning of stereotactic brain patients with the aid of real-time CT image guidance.

This note presents a method that recalculates the coordinates of the isocentre for patients undergoing stereotactic radiotherapy to the brain with a relocatable head frame based on a pre-treatment CT scan. The method was evaluated by comparing initial stereotactic coordinates of the isocentre with the recalculated coordinates for eight single-fraction patients. These patients had the Brown-Roberts-Wells (BRW) frame fixed to the outer table of the skull, and therefore the coordinates of any anatomical point should be identical between the initial scan and the pre-treatment scan. The differences between the two sets of coordinates were attributed to errors in the method. The results showed that the systematic errors in the recalculated coordinates were less than 0.05 mm, and they were not statistically significant. The random errors (one standard deviation) were from 0.35 mm (lateral) to 0.58 mm (vertical). The average value of the combined 3D difference was 0.75 mm.

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

BACKGROUND: The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. METHODS: To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. RESULTS: This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. CONCLUSION: The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

Daily target localization for prostate patients based on 3D image correlation.

There are several localization techniques that have been used for prostate treatment. Recently, the potential use of a variety of CT-based equipment in the treatment room has been discussed. The goal of our study was to develop an automated procedure for daily treatment table shift calculation based on two CT data sets: simulation CT data and localization CT data. The method suggested in this study is a 3D image cross-correlation of small regions of interest (ROI) within the two data sets. The relative position of the two ROIs with respect to each other is determined by the maximum value of the normalized cross-correlation function, calculated for all possible relative locations of the two ROIs. After the best match is found the shifts are given by the vector connecting the treatment isocentre and the planning isocentre (both determined by the radio opaque fiducial markers on the patient's skin). The results have been compared with shifts calculated through manual fusion. The shift differences, averaged over 17 statistically independent shift calculations, are less then 1 mm in the lateral and longitudinal directions, and about 1 mm in the AP direction. The impact of image noise on the performance of the algorithm has been tested. The results show that the algorithm accurately adjusts for target positional changes even with Gaussian noise levels as high as 20% inserted.

Stereotactic IMRT for prostate cancer: dosimetric impact of multileaf collimator leaf width in the treatment of prostate cancer with IMRT.

The focus of this work is the dosimetric impact of multileaf collimator (MLC) leaf width on the treatment of prostate cancer with intensity-modulated radiation therapy (IMRT). Ten patients with prostate cancer were planned for IMRT delivery using two different MLC leaf widths--4mm and 10mm--representing the Radionics micro-multileaf collimator (mMLC) and Siemens MLC, respectively. Treatment planning was performed on the XKnifeRT2 treatment-planning system (Radionics, Burlington, MA). All beams and optimization parameters were identical for the mMLC and MLC plans. All the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose. The differences in dose distribution between the two different plans were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. We specifically compared the volume of rectum receiving 40 Gy (V40), 50 Gy (V50), 60 Gy (V60), the dose received by 17% and 35% of rectum (D17 and D35), and the maximum dose to 1 cm3 of the rectum for a prescription dose of 74 Gy. For the urinary bladder, the dose received by 25% of bladder (D25), V40, and the maximum dose to 1 cm3 of the organ were recorded. For PTV we compared the maximum dose to the "hottest" 1 cm3 (Dmax1 cm3) and the dose to 99% of the PTV (D99). The dose inhomogeneity in the target, defined as the ratio of the difference in Dmax1 cm3 and D99 to the prescribed dose, was also compared between the two plans. In all cases studied, significant reductions in the volume of rectum receiving doses less than 65 Gy were seen using the mMLC. The average decrease in the volume of the rectum receiving 40 Gy, 50 Gy, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p < 0.0001 for V40 and V50 and p < 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum using the mMLC were 20.4% (p < 0.0001) and 18.3% (p < 0.0002), respectively. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 29%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cm3 of the rectum between the two plans for all cases (p > 0.78). In conclusion, the use of the mMLC for IMRT of the prostate resulted in significant improvement in the DVH parameters of the prostate and critical organs, which may improve the therapeutic ratio.

Radiotherapy patterns of care study in lung carcinoma.

PURPOSE: For the first time, a lung Patterns of Care Study was conducted to determine the national patterns of radiation (RT) practice in patients treated for nonmetastatic lung cancer in 1998 to 1999. MATERIALS AND METHODS: A national survey of randomly selected RT institutions in the United States was conducted using two-stage cluster sampling, stratified by practice type. Patients with nonmetastatic lung cancer (Karnofsky performance score [KPS] > or = 60), who received RT as definitive or adjuvant therapy, were randomly selected. To determine national estimates, sample size was weighted by the relative number of institutions per strata and the number of patient records reviewed per the number of patients eligible. Accordingly, 42,335 patient records from 58 institutions were reviewed by trained research associates. The unweighted sample size (or number of patients) was 541. RESULTS: The histologies were small-cell lung cancer (SCLC) in 14.5% of patients versus non-small-cell lung cancer (NSCLC) in 85.5% of patients. The median age was 67 years (range, 29 to 92 years); 61% of patients were male, and 38% were current smokers. Bone scans and brain imaging were not obtained in 34% and 52% of clinical stage (CS) III NSCLC patients, respectively. Regarding treatment strategies, for SCLC and CS III NSCLC, chemotherapy plus RT was used significantly more than RT alone (P <.05); in CS I NSCLC, RT alone was the primary treatment (P <.05). Overall, 58% of patients received systemic therapy. On multivariate analysis, factors correlating with increased use of chemotherapy included younger age, histology (SCLC > NSCLC), increasing CS, increasing KPS, and lack of comorbidities. Only 3% of all patients were treated on prospective clinical trials. CONCLUSION: This study establishes the general patterns of care for lung carcinoma in RT facilities within the United States. As supported by clinical trials, patients with limited-stage SCLC and CS III NSCLC received chemotherapy plus RT more than they received RT alone. Further improvements in staging, smoking cessation, and increased accrual to clinical trials must be encouraged.

Randomized phase II chemotherapy and radiotherapy trial for patients with locally advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92-04.

PURPOSE: The standard treatment for patients with locally advanced inoperable non-small-cell lung cancer and good prognostic factors has become combined chemotherapy (ChT) and radiotherapy (RT). However, the sequencing of the two modalities, as well as fractionation of RT, has been controversial. The Radiation Therapy Oncology Group (RTOG) Study 92-04 was a randomized Phase II study designed to evaluate further the toxicity and efficacy of 2 different strategies of chemoradiation evaluated in 2 prior RTOG Phase II studies. METHODS: Patients with Stage II or III medically inoperable or unresectable non-small-cell lung cancer, good performance status, and minimal weight loss were enrolled into a prospective randomized Phase II RTOG study. Arm 1 consisted of induction ChT (vinblastine 5 mg/m(2) i.v. bolus weekly for the first 5 weeks, and cisplatin, 100 mg/m(2) i.v. on Days 1 and 29) followed by concurrent ChT/RT (cisplatin 75 mg/m(2) i.v. on Days 50, 71, and 92) during thoracic radiotherapy (63 Gy in 34 fractions during 7 weeks starting on Day 50). Arm 2 was concurrent ChT and hyperfractionated RT starting on Day 1 with a total dose of 69.6 Gy in 58 fractions during 6 weeks, 1.2 Gy/fraction b.i.d. ChT consisted of cisplatin, 50 mg/m(2) i.v. on Days 1 and 8, and oral VP-16, 50 mg b.i.d. for 10 days only on the days of thoracic radiotherapy repeated on Day 29. RESULTS: A total of 168 patients were entered between 1992 and 1994, and 163 patients were eligible for analysis. Eighty-one patients were treated in Arm 1 and 82 patients in Arm 2. Pretreatment characteristics, including age, gender, Karnofsky performance status, histologic features, and stage, were similar. The incidence of acute esophagitis was significantly higher among patients treated in Arm 2 than among those treated in Arm 1 (p <0.0001). The incidence of acute hematologic toxicity was significantly higher among patients treated in Arm 1 (p = 0.01 for anemia and p = 0.03 for other hematologic toxicities) than among those treated in Arm 2. Analysis of late toxicity showed that chronic esophageal toxicity was significantly more frequent in Arm 2 than in Arm 1 (p = 0.003). The time to in-field progression was significantly different (p = 0.009), favoring Arm 2 compared with Arm 1 (26% vs. 45% with failure in 2 years and 30% vs. 49% with failure in 4 years, respectively). The median 2-year and overall 5-year survival rates were similar between the two arms. CONCLUSION: Concurrent ChT and hyperfractionated RT resulted in a significant prolongation of the time to in-field progression, but with higher acute and chronic esophagitis. No other significant differences were observed between the two groups. Investigation with a chemoradio-protector is under way.

Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations.

PURPOSE: To quantify the extent of neuronal cell loss imparted to the brain by means of radiation therapy through the decline of the amino acid derivative N-acetylaspartate (NAA) by using proton (hydrogen 1) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Proton MR spectroscopy in a clinical MR imager was used to ascertain the amount of whole-brain NAA before and immediately after whole-brain radiation therapy 3-4 weeks later. Eight patients (four women, four men; median age, 55 years; age range, 39-70 years) were studied. All subjects had lung cancer (non-small cell lung cancer [n = 5], small-cell lung cancer [n = 3]) and received either palliative or prophylactic whole-brain radiation therapy. Six of them also underwent a Mini-Mental Status Examination (MMSE) for correlation with the whole-brain NAA. Two-tailed Student t tests were used to evaluate the data. RESULTS: A significant (P = .042) average decline in whole-brain NAA of -0.91 mmol per person was observed in the cohort. No corresponding changes occurred in MMSE scores. There was no significant difference in whole-brain NAA decline between prophylactic and therapeutic whole-brain radiation therapy. CONCLUSION: Since whole-brain NAA loss was detected even when MMSE scores were unchanged, the former seems to be a more sensitive measure of radiation therapy injury than is the latter.

Hypoxia in human prostate carcinoma: an Eppendorf PO2 study.

The purpose of this study was to characterize the extent of hypoxia in human prostate carcinoma using the Eppendorf PO2 microelectrode. Custom-made Eppendorf PO2 microelectrodes were used to obtain PO2 measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies), as well as from a region of normal muscle for comparison. Fifty-nine patients with localized prostate cancer were studied, all of whom received brachytherapy implants under spinal anesthesia. A multivariate mixed effects analysis for prediction of tumor oxygenation was performed including the following covariates: type of tissue (prostate versus muscle), prostatic-specific antigen, disease stage, patient age and race, tumor grade, volume, perineural invasion, and hormonal therapy. Because of differences in patient characteristics, control measurements were obtained from normal muscle in all patients. This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median PO2 = 2.4 mm Hg) compared with the measurements from normal muscle (average median PO2 = 30.0 mm Hg), p < 0.0001. A multivariate, linear, mixed analysis demonstrated that the only significant predictor of oxygenation was the type of tissue (prostate versus muscle). This study, using in vivo electrode oxygen measurements, suggests that hypoxia exists in human prostate carcinoma. More patients will be accrued to this study to ultimately correlate the oxygenation status in prostate carcinoma tumors with treatment outcome.

Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme.

PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively. Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly modest, despite considerably higher overall dose intensity, compared to that achievable in other disease sites. Median survival by RPA class without prolonged adjuvant therapy is comparable to RTOG controls treated with standard EBRT and BCNU (1 year of BCNU).

To move or not to move: measurements of prostate motion by urethrography using MRI.

PURPOSE: Urethrography is commonly used to aid in definition of the prostate apex during CT simulation for prostate cancer. If the position of the prostate were altered by the urethrogram itself, then systematic error could be introduced into the patient's treatment. Sagittal MRI scans were acquired immediately before and after a localization urethrogram to determine the extent of displacement. METHODS AND MATERIALS: Thirteen patients underwent sagittal T2-weighted fast spin echo MRI scans. Patients were scanned supine in an alpha cradle cast in the treatment position. The prostate was contoured by 3 different observers to determine the apex location on the central sagittal MRI section and the center of mass relative to an immobile bony landmark. Statistical multivariate analysis was performed to establish if there was a net displacement of the prostate (systematic error), and to determine the margin required to cover the random prostate position within a 95% confidence interval. RESULTS: There was no significant systematic motion of either the prostate nor its apex in either the anterior-posterior or superior-inferior directions. The average motion of the prostate center of mass was 0.04 +/- 0.40 cm (1 SD) and 0.01 +/- 0.33 cm in the anterior-posterior and superior-inferior direction, respectively. The corresponding figures for location of the apex were 0.05 +/- 0.30 cm and 0.01 +/- 0.33 cm, respectively. The statistical analysis revealed that a margin of 2 mm is sufficient to cover any random motion of the prostate that could occur as a result of the urethrogram 95% of the time. CONCLUSION: Urethrography during CT simulation for prostate cancer does not cause significant prostate displacement or systematic error in planning and delivering external-beam radiation.