Search

Purpose: To quantify the variations in the length and position of fiducial markers induced by motion in axial (ACT), helical (HCT) and cone-beam CT (CBCT) imaging and associated uncertainty in image-guided radiotherapy (IGRT) by measurement and modeling., Methods: A mobile thorax phantom containing markers of various lengths was imaged using ACT, HCT and CBCT imaging. The phantom was imaged while stationary and moving where it was moved sinusoidally with different motion amplitudes and frequency. An analytical motion model was developed that predicts the localization accuracy of IGRT based on fiducial markers in mobile phantom with ACT, HCT and CBCT., Results: The apparent lengths of the markers varied with the different motion patterns and CT imaging modalities. In CBCT, the apparent length of the markers increased linearly with the motion amplitude for both half-fan and full-fan modes. In HCT and ACT, the apparent length of the markers increased or decreased non-linearly with motion parameters and speed of the imaging couch. When the marker moved opposed to couch motion the apparent lengths decreased, while they increased when the phantom moved along the direction of the imaging couch as predicted by the motion model. The position of marker centers did not shift and distance between makers did not change in CBCT images. However, in HCT and ACT, the position of marker center and distance between markers varied depending on motion parameters during imaging. The marker center could move superiorly or inferiorly and the distance between markers could increase or decrease depending on the phase of motion as predicted by the motion model., Conclusions: The variations of marker length and position due to phantom motion were quantified by measurement and modeling. These variations may lead to large positioning uncertainties in patient setup and tumor localization based on IGRT with fiducial marker registration.

We compared treatment plan quality based on target coverage and normal brain tissue sparing for two intracranial stereotactic radiosurgery systems: TrueBeam STx using VMAT and Gamma Knife (GK). Ten patients with 24 tumors (seven with 1-2 and three with 4-6 ranging from 0.1 to 20.2 cc), previously treated with GK Model 4C (prescription doses ranging from 14-23 Gy), were re-planned for VMAT using Eclipse treatment planning system. Various photon beam energies and MLC leaf widths with and without jaw tracking were studied to achieve optimal plans. Plan qualities were assessed by target coverages using Paddick Conformity Index (PCI), normal-brain-tissue integral dose (Gy-cc) and sparing. In all cases critical structure dose criteria were met. The average PCI was 0.76±0.21 for VMAT and 0.46±0.20 for GK plans (p≤0.001), respectively. On average 81% reduction of 12 Gy normal-brain-tissue volumes was achieved by VMAT. The average integral dose ratio of GK to VMAT plans was 1.50±0.61 (p=0.006). VMAT was capable of producing higher quality treatment plans in terms of target coverage and normal brain tissue sparing than GK while using optimal beam geometries and optimization techniques., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have no conflicts of interest to report.

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment., (Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate quantitatively the deformation of the mammosite balloon, eccentricity of the source position and their effects on the dose delivered to the tumor lumpectomy site and critical structures., Materials and Methods: The distances of the brachytherapy source to the surface of the mammosite balloon were measured in using radiographic images for fractions 1 to 10 for twelve patients. The dose at the balloon surface (nearly 680cGy) and prescription dose of 340cGy at 1cm from the balloon surface were calculated for the different fractions and their dependence on the balloon volume and source position were investigated., Results: The position of the source can be offset from the center of the mammosite balloon by up to 6mm. Deformation of the balloon led to variations in its dimensions by up to 8mm. The dose at 1cm from the balloon surface that covers the lumpectomy site varied by up to 19% from 340cGy along the elongated diameter of the balloon and by up to 40% along the short diameter. Maximal doses to the skin, ribs and lung were 420cGy, 630cGy and 500cGy per fraction, respectively, which depended mostly on their distance from the balloon surface., Conclusion: The geometric variations in the shape of the balloon and position of the source can cause lack of dose coverage to the lumpectomy site or create hot dose spots in the surrounding normal tissue that might compromise intended clinical goals. Users as well as vendors should consider correction measures for the deformation of the balloons and the eccentricity of the position of the high dose source.

Introduction: CNS metastasis (CNSmet) with gynecologic malignancy (GM) is associated with poor prognosis and symptom burden. Two prognostic indices, the recursive partitioning analysis (RPA) and graded prognostic assessment (GPA), used in other solid tumors to guide intervention options were evaluated among GM patients., Methods: Retrospective chart review was performed to identify patients with primary GM diagnosed with CNSmet from 2005-2014. RPA and GPA were applied and evaluated for goodness of fit. Long-term survivors (LTS) were those with survival time from CNSmet ≥9 months., Results: 35 patients were identified with median age of 62 years (range, 41-78). The majority had ovarian cancer (54%). Median survival was 4.5 months (0.1-25.9), and median time from initial diagnosis was 2.6 years (0-19.6). Presenting symptoms varied but headache (57%) and altered mental status (23%) were most common. 37% had a solitary CNS lesion, 31% had 2-8, and 31% >8. 57% were treated with WBRT, 14% with stereotactic radiosurgery (SRS), and 20% with combinations of treatments, and 2 elected for hospice. 27% (9/33) of the patients were LTS. The GPA was not significantly associated with patient outcome (p=0.46). The RPA predicted time to death (p=.0010)., Conclusion: Prognostic indices used to guide therapeutic interventions perform poorly in GM. Detection and aggressive symptom management are critical in maintaining QOL. Multidisciplinary consultation is critical to optimize outcomes and symptom control., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess quantitatively elongation of mobile targets in cone-beam CT (CBCT) imaging by measurement and modeling. A mathematical model was derived that predicts the measured lengths of mobile targets and its dependence on target size and motion patterns in CBCT imaging. Three tissue-equivalent targets of differing sizes were inserted in an artificial thorax phantom to simulate lung lesions. Respiratory motion was mimicked with a mobile phantom that moves in one-dimension along the superior-inferior direction at a respiration frequency of 0.24 Hz for eight different amplitudes in the range 0-40 mm. A mathematical model was derived to quantify the variations in target lengths and its dependence on phantom motion parameters in CBCT. Predictions of the model were verified by measurement of the lengths of mobile targets in CBCT images. The model predicts that target lengths increased linearly with increase in speed and amplitude of phantom motion in CBCT. The measured lengths of mobile targets imaged with CBCT agreed with the calculated lengths within half-slice thickness spatial resolution. The maximal length of a mobile target was independent of the frequency and phase of motion. Elongation of mobile targets was similar in half-fan and full-fan CBCT for similar motion patterns, as long as the targets remained within the imaging view. Mobile targets elongated linearly with phantom speed and motion amplitude in CBCT imaging. The model introduced in this work assessed quantitatively the variation in target lengths induced by motion, which may be a useful tool to consider elongations of mobile targets in CBCT applications in diagnostic imaging and radiotherapy.

The purpose of this study is to determine the dependency of the planned dose perturbation (PDP) algorithm (used in Sun Nuclear 3DVH software) on spatial resolution of the MapCHECK 2 detectors. In this study, ten brain (small target), ten brain (large target), ten prostate, and ten head-and-neck (H&N) cases were retrospectively selected for QA measurement. IMRT validation plans were delivered using the field-by-field technique with the MapCHECK 2 device. The measurements were performed using standard detector density (standard resolution; SR) and a doubled detector density (high resolution; HR) by merging regular with shifted measurements. SR and HR measurements were fed into the 3DVH software and ROI (region of interest), planning target volume (PTV), and organ at risk (OAR)) dose statistics (D95, Dmean, and Dmax) were determined for each. Differences of the dose statistics normalized to prescription dose for ROIs between original planning and PDP-perturbed planning were calculated for SR (ΔDSR) and HR (ΔDHR), and difference between ΔDSR and ΔDHR (ΔDSR-HR = ΔDSR - ΔDHR) was also calculated. In addition, 2D and 3D γ passing rates (GPRs) were determined for both resolutions, and a correlation between GPRs and ΔDSR or ΔDHR for PTV dose metrics was determined. No considerably high mean differences between ΔDSR and ΔDHR were found for almost all ROIs and plans (< 2%); however, |ΔDSR|, |ΔDHR|, and |ΔDSR-HR| for PTV were found to significantly increase as the PTV size decreased (e.g., PTV size < 5 cc). And statistically significant differences between SR and HR were observed for OARs proximal to targets in large brain target and H&N cases. As plan modulation represented by fractional MU/prescription dose (MU/cGy) became more complex, the 2D/3D GPRs tended to decrease; however, the modulation complexity did not make any noticeable distinctions in the DVH statistics of PTV between SR and HR, excluding the small brain cases whose PTVs were extremely small (PTV = 11.0 ± 10.1 cc). Moderate to strong negative correlations (-1 < r < -0.3) between GPRs and PTV dose metrics indicated that small clinical errors for PTV occur at the higher GPRs. In conclusion, doubling the detector density of the MapCHECK 2 device is recommended for small targets (i.e., PTV < 5 cc) and multiple targets with complex geometry with minimum setup error in the DVH-based plan evaluation.

THIS STUDY WAS PERFORMED TO EVALUATE DOSIMETRIC DIFFERENCES BETWEEN CURRENT INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY MODES: Step-and-shoot (SS), sliding window (SW), and volumetric modulated arc therapy (VMAT). Plans for 15 prostate cancer patients with 10 MV photon beams using each IMRT mode were generated. Patients had three planning target volumes (PTVs) including prostate, prostate plus seminal vesicles, and pelvic lymphatics. Dose volume histograms (DVHs) of PTVs and organs at risk (OARs), tumor control probability (TCP) and normal tissue complication probabilities (NTCPs), conformation number, and monitor units (MUs) used were compared. Statistical analysis was performed using the analysis of variance (ANOVA) technique. The TCPs were < 99% with insignificant differences among modalities (P > 0.99). Doses to all critical structures were higher on average with SW method compared to SS, but insignificant. NTCP values were lowest for VMAT in all structures excepting bladder. Normal tissue volumes receiving doses in the 20-30 Gy range were reduced for VMAT compared to SS. Percentage of MUs required for VMAT to deliver a comparable plan to SS and SW was at least 40% less. In conclusion, similar target coverage and normal tissue doses were found by the three compared modes and the dosimetric differences were small.

Purpose: To investigate enlargement of prostate volume by edema during brachytherapy seed implantation and develop a nomogram model to calculate air-kerma strength (AKS) required for implantation of the enlarged transient prostatic volume., Materials and Methods: The prostate volume was measured prior and after seed implantation using trans-rectal ultrasound imaging in the operating room to obtain volume enlargement. A nomogram model was developed that calculates AKS required for implantation of the enlarged transient prostate volume with optimal dose coverage., Results: The measured prostate enlargement in this study was up to 60% of the initial volume. The effective prostatic volume enlargement was calculated for three isotopes: 125I, 103Pd and 131Cs. The effective volume enlargement for 125I implants was relatively small (< 10%) because of its long half-life. For 103Pd and 131Cs with short half-lives, additional AKS up to 20% and 30%, respectively, might be required to provide appropriate dose coverage of possible enlarged prostatic volumes., Conclusions: Prostate volume enlargement should be considered to obtain optimal dose coverage particularly for short half-life isotopes such as 131Cs and 103Pd. The nomogram model developed in this work provides the AKS required for implants with a wide range of prostatic volume enlargements (5-100%) for three isotopes., Keywords: prostate brachytherapy; nomogram; air-kerma strength; edema; volume enlargement.

The purpose of this study was to evaluate the impact of daily setup error and interfraction organ motion on the overall dosimetric radiation treatment plans. Twelve patients undergoing definitive intensity-modulated radiation therapy (IMRT) treatments for prostate cancer were evaluated in this institutional review board-approved study. Each patient had fiducial markers placed into the prostate gland before treatment planning computed tomography scan. IMRT plans were generated using the Eclipse treatment planning system. Each patient was treated to a dose of 8100 cGy given in 45 fractions. In this study, we retrospectively created a plan for each treatment day that had a shift available. To calculate the dose, the patient would have received under this plan, we mathematically "negated" the shift by moving the isocenter in the exact opposite direction of the shift. The individualized daily plans were combined to generate an overall plan sum. The dose distributions from these plans were compared with the treatment plans that were used to treat the patients. Three-hundred ninety daily shifts were negated and their corresponding plans evaluated. The mean isocenter shift based on the location of the fiducial markers was 3.3 ± 6.5 mm to the right, 1.6 ± 5.1 mm posteriorly, and 1.0 ± 5.0 mm along the caudal direction. The mean D95 doses for the prostate gland when setup error was corrected and uncorrected were 8228 and 7844 cGy (p < 0.002), respectively, and for the planning target volume (PTV8100) was 8089 and 7303 cGy (p < 0.001), respectively. The mean V95 values when patient setup was corrected and uncorrected were 99.9% and 87.3%, respectively, for the PTV8100 volume (p < 0.0001). At an individual patient level, the difference in the D95 value for the prostate volume could be >1200 cGy and for the PTV8100 could approach almost 2000 cGy when comparing corrected against uncorrected plans. There was no statistically significant difference in the D35 parameter for the surrounding normal tissue except for the dose received by the penile bulb and the right hip. Our dosimetric evaluation suggests significant underdosing with inaccurate target localization and emphasizes the importance of accurate patient setup and target localization. Further studies are needed to evaluate the impact of intrafraction organ motion, rotation, and deformation on doses delivered to target volumes., (Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor., Methods and Materials: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months., Results: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement of preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients., Conclusions: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Review our institutional outcomes with linear accelerator based stereotactic radiation therapy at the University of Oklahoma., Methods: We retrospectively reviewed all patients treated in our department with linear accelerator based stereotactic radiation therapy since we implemented this modality in 2008. Thirty-seven patients have been treated with a mean follow-up of 8.3 months. Seventeen patients had tumors near critical structures; ten had treatment sites not suited for gamma knife therapy. Outcomes are reviewed for efficacy and toxicity., Results: Acute and long term complications reported are minimal. Stabilization of treatment sites was achieved in 96% of patients on follow-up imaging. Thirteen patients (35%) have died, of which eleven died to systemic disease progression outside of the treatment site. No treatment related deaths occurred., Conclusions: Stereotactic radiation therapy is a successful treatment modality to achieve local disease control with minimal toxicity. We plan to expand its use and applications in the future.

Objectives: Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer., Methods: Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions., Results: Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events., Conclusions: Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.

The purpose of this study was to evaluate setup accuracy and quantify random and systematic errors of the BrainLAB stereotactic immobilization mask and localization system using kV on-board imaging. Nine patients were simulated and set up with the BrainLAB stereotactic head immobilization mask and localizer to be treated for brain lesions using single and hypofractions. Orthogonal pairs of projections were acquired using a kV on-board imager mounted on a Varian Trilogy machine. The kV projections were then registered with digitally-reconstructed radiographs (DRR) obtained from treatment planning. Shifts between the kV images and reference DRRs were calculated in the different directions: anterior-posterior (A-P), medial-lateral (R-L) and superior-inferior (S-I). If the shifts were larger than 2mm in any direction, the patient was reset within the immobilization mask until satisfying setup accuracy based on image guidance has been achieved. Shifts as large as 4.5 mm, 5.0 mm, 8.0 mm in the A-P, R-L and S-I directions, respectively, were measured from image registration of kV projections and DRRs. These shifts represent offsets between the treatment and simulation setup using immobilization mask. The mean offsets of 0.1 mm, 0.7 mm, and -1.6 mm represent systematic errors of the BrainLAB localizer in the A-P, R-L and S-I directions, respectively. The mean of the radial shifts is about 1.7 mm. The standard deviations of the shifts were 2.2 mm, 2.0 mm, and 2.6 mm in A-P, R-L and S-I directions, respectively, which represent random patient setup errors with the BrainLAB mask. The Brain-LAB mask provides a noninvasive, practical and flexible immobilization system that keeps the patients in place during treatment. Relying on this system for patient setup might be associated with significant setup errors. Image guidance with the kV on-board imager provides an independent verification technique to ensure accuracy of patient setup. Since the patient may relax or move during treatment, uncontrolled and undetected setup errors may be produced with patients that are not well-immobilized. Therefore, the combination of stereotactic immobilization and image guidance achieves more controlled and accurate patient setup within 2mm in A-P, R-L and S-I directions.

Purpose: To investigate the increase in surface dose under immobilization thermoplastic masks by measurements and calculation in the build-up region using Gafchromic films and Monte Carlo simulation., Materials and Methods: Surface doses were measured underneath three thermoplastic masks in open fields using 6 and 18 MV photon beams. These masks are used to immobilize patients for head and neck (H&N), pelvis and thoracic treatment. Gafchromic EBT films were placed on the top of the flat surface of a phantom partially underneath the mask and exposed in open 10 x 10 cm2 photon fields. The depth doses were calculated using BEAMnrc Monte Carlo code for water-equivalent film detectors with different layers of thickness ranging from 50 microm to 2.5 mm and compared with film measurements., Results: Surface dose increased by a factor of 3 to 4 underneath the mask relative to the open areas and 6 MV beam delivers more skin dose than 18 MV. H&N mask increased surface dose by a factor of 3 using 18 MV and a factor of 4 using 6 MV. In addition, increase in surface dose depended on the type of the mask, the size of openings, and the amount of stretching performed during the mask preparation. The measured depth doses were compared with BEAMnrc Monte Carlo calculation for water-equivalent detectors using different sizes. The calculated depth dose depended significantly on the thickness of film detector and varies by more than 15% using layer thickness of 2.5 mm compared to 50 microm. Surface doses measured by Gafchromic EBT films agreed within 3% with the Monte Carlo calculations using a small detector layer of 50 microm., Conclusion: Thermoplastic masks used for patient immobilization can significantly increase skin doses by up to a factor of 4 more than that without the mask using 6 MV beams. The skin reactions resulting from thermoplastic masks should be monitored and corrective measures should be taken during treatment such as partially removing the mask over skin areas with complications and optimizing the skin dose in IMRT planning. Gafchromic EBT films provide accurate skin dosimetry which agrees within 3% with Monte Carlo calculations. Gafchromic EBT film makes an excellent tool for measuring depth doses in the buildup region and these data can be applied for treatment planning calculations and IMRT optimization.

This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm(3) on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed implants. Here, we introduced a new approach based on the use of post-implant US twister images to correct for prostate enlargement intra-operatively. Besides the ability to localize the seeds and superior soft tissue visibility, the twister US images include effects of the enlargement of the prostate gland and seed migration during the implantation procedure.

Primary nonHodgkin's lymphoma (NHL) occurs in both nodal and extranodal sites. Lymphoma arising in mammary tissue is rare. The majority are of B-cell origin, while a few case studies of T-cell lymphomas of the breast have been reported. The clinical and histologic features of a 74-year-old female diagnosed with T-cell mammary lymphoma are reported, as well as her treatment course and follow-up. A literature review is included. We conclude primary low-grade T cell lymphoma of the breast can be treated with conservative surgery followed by involved field radiation therapy.

The purpose of this report was to study the results of external beam radiotherapy for patients with extranodal stage IA non-Hodgkin's lymphoma (NHL). A retrospective review was carried out on 27 patients seen between 1984 and 1998 with stage IA NHL of extranodal sites, and followed up for a minimum of 1 year. Sites involved included eye/orbit (seven), parotid (five), breast (four), Waldeyer ring (four), thyroid (three), other head and neck (two), stomach (one), and prostate (one). All patients had biopsy-proven disease and underwent staging workup to rule out other sites of disease. Histologic analysis revealed 16 patients with low-grade NHL, 9 with intermediate-grade, and 2 with high-grade. Ten patients received chemotherapy before radiation therapy, and eight of them had a complete response. The remaining 17 patients were treated with external beam radiation therapy alone. Radiation was directed to the involved field at 1.8 Gy to 2.0 Gy per fraction to a median dose of 40 Gy (range: 20-50.4 Gy). The median patient age was 71 years (range: 39-85 years); 55% were female, and 45% were male. A complete response was attained in all 27 patients after radiation therapy. There were five failures (all in uninvolved distant sites), and two deaths during the follow-up. Median disease free survival (DFS) and overall survival (OS) have not been reached. The 5-year DFS and OS are 85% and 94%, respectively. Older age at presentation showed a trend toward worse outcome (p = 0.07), but because of the relatively few events, other factors (radiation dose, grade of disease, sex, or the use of chemotherapy) showed no statistical differences among the patients. External beam radiation therapy is a highly effective treatment for stage IA NHL found in extranodal sites.

Background: The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma., Methods: Twenty-six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6-104 ng/mL). All patients received external beam radiation therapy using a four-field technique. The median radiation dose was 6,800 centigrays (cGy) given in 200-cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 degrees C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan-Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow-up for all patients was 71 months., Results: The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%, respectively, and the median and 5-year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06)., Conclusions: The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted., (Copyright 2000 American Cancer Society.)

To evaluate treatment outcome and morbidity of stereotactic external-beam irradiation (SEBI) in pediatric patients, we reviewed 14 children treated with SEBI, using a 10-MV isocentric linear accelerator at McGill University between 1988 and 1994. The median follow-up was 46 months (range 6-82 months). The median age was 14 years. There were 8 low-grade astrocytomas, 3 neuromas and 4 other histologies. Twelve patients received fractionated treatments. The median collimator diameter was 2.5 cm (range 1-5 cm). The median biological effective dose delivered to the entire tumor volume was 57 Gy for astrocytomas and 43 Gy for the other histologies. The overall actuarial survival rate and disease-free survival rate at 5 years were 83 and 62%, respectively. For the patients with low-grade astrocytomas, the 5-year survival and disease-free survival rates were 100 and 60%, respectively. Four children had recurrence at a median of 37 months. Four patients developed treatment-related complications: 1 had edema alone, 2 had necrosis and 1 had edema associated with necrosis. Neither the physical nor radiobiological parameters were predictive of the treatment outcome or the treatment complications. Stereotactic irradiation is a valid option for progressive nonresectable tumors in children., (Copyright 1999 S. Karger AG, Basel)

To determine if there is a subgroup of patients with pretreatment PSA > or = 20 ng/ml with a favorable outcome after external beam radiation therapy. We analyzed retrospectively treatment outcomes of 129 patients with pretreatment PSA > or = 20 ng/ml treated in our department from 2/88-8/94. Median patient age was 70 years (range 51-89 years). Tumor stage was T1/T2ab in 68, T2c/T3 in 61 patients. Initial Gleason grade was < 7 in 82 and > or = 7 in 47 patients. Median PSA was 35 ng/ml (mean 45 ng/ml, range 20-191 ng/ml). Ninety-seven patients received four-field conformal external beam radiation therapy. No patient received surgery or hormonal therapy prior to treatment. Median central axis dose was 73 Gy (range 68-79 Gy). Covariates considered in univariate and multivariate analyses included central axis dose, pretreatment PSA, presence of perineural invasion, Gleason score, palpable tumor stage and patient age. bNED failure was defined as a PSA > or = 1.5 and rising on two consecutive determinations. Median follow up was 50 months (range 3-100 months). Overall bNED control for the entire patient population was 22% at five years. Of the covariates analyzed, dose (P < 0.01), stage (P < 0.01), Gleason Score (P < 0.01), and the presence of PNI (P = 0.01) were significant on multivariate analysis. Based on these results, patients could be stratified into two distinct groups. Group I consisted of 19 patients with favorable features including T1/T2ab disease, Gleason Score 2-6, no perineural invasion treated to a dose > 73 Gy to the central axis. Patients in Group II had at least one of the above poor prognostic features or were treated to central axis doses < 73 Gy. The bNED control was significantly higher for patients in Group I than those in Group II (58% vs. 23%, P = 0.0027). There appears to be a favorable subgroup of patients with PSA > or = 20 ng/ml where treating to doses over 73 Gy to the central axis is warranted (four-year bNED rate of 58%). However, because of the small patient numbers, these results will need to be validated with longer follow up.

To examine the early determinants of cortical cytoarchitecture, we deleted specific neuronal classes in the primate visual cortex by ionizing irradiation at selected prenatal stages. Multiple doses of X-rays were delivered to the macaque monkey brain between embryonic day (E) 80 and E90 to block the division of cells destined to populate the superficial cortical layers, between E70 and E79 to eliminate neurons destined for the middle layers; and between E33 and E40 to delete neurons destined for the lateral geniculate nucleus (LGN) that project to the cortex. All animals were killed after birth, and their brains were processed for histological and electron microscopic analyses. Cell density and number in the LGN and visual cortex were determined by using three-dimensional, computer-aided morphometry. In animals irradiated with low doses (total of approximately 200 cGy) during the genesis of the LGN but before the onset of corticogenesis (E33-40), the LGN was reduced in both volume and number of neurons. Area 17 in these animals displayed only slight changes in cortical thickness, cell density, and area-specific cytoarchitectonic features, whereas the total surface devoted to area 17 was significantly diminished. In contrast, animals irradiated with low doses during the period of corticogenesis, after the completion of the LGN genesis, showed no significant change in the volume of the LGN or in the number of its cells. Moreover, in these animals, the surface of area 17 was not significantly altered, although the cortical layers generated at the time of irradiation had a significantly lower density and total number of cells, whereas the layers generated before and after the period of irradiation were spared. In contrast, cases exposed to high doses of X-ray (total > 300 cGy) showed more severe effects, including all layers. However, layers normally generated during irradiation were depleted and consisted of cell-sparse strata populated by densely packed neuropil (axons, small dendrites, dendritic spines, and synaptic boutons). These cell-sparse strata were situated deeper in the early irradiated animals than in the later irradiated animals, and their laminar position changed abruptly at the area 17/18 border. These results show that low doses of irradiation in a slowly developing primate brain can be used effectively to eliminate targeted classes of neurons before they reach their final position, providing an opportunity to examine the role of cell-cell interactions in the formation of circuitry and the role of specific cell classes in cortical development.

Radiation-induced apoptosis detected by gel electrophoresis was measured in cells of three human prostate carcinoma cell lines (TSU, PC-3 and DU-145) and compared to their intrinsic radiosensitivities as measured by clonogenic assays. The intrinsic radiosensitivities of each cell line were defined by their alpha and beta coefficients and their surviving fraction at 2 Gy, derived from complete survival curves. The temporal expression and kinetics of radiation-induced apoptosis for DU-145 cells, the human prostate carcinoma cell line which expressed the highest rate of radiation-induced apoptosis, was characterized further by differential sedimentation and the immunofluorescence assay (Apoptag) which was specific for 3'-OH ends in cellular DNA. Cell viability was measured microscopically with trypan blue staining. Cell survival after various doses was computer-fitted to either a simple linear or a linear-quadratic equation. Twenty-four hours after a 10-Gy dose of 137Cs gamma rays, DNA fragmentation to nucleosome multimers was strongly expressed in only DU-145 cells. In this cell line, when centrifugation at 12,000g for 10 min was used to separate fragmented from large molecular weight DNA, the proportion of DNA in the supernatant increased to a maximum of approximately 17% of the total by 10-12 h after radiation treatment. Cell death 24 h after irradiation measured by trypan blue exclusion assays followed single-hit kinetics up to 80 Gy. The proportion of cells which were labeled with Apoptag displayed single-hit kinetics and yielded the same inactivation coefficient as measured by trypan blue. Together, these data indicate that the rapid (24 h) inactivation of irradiated DU-145 cells results from apoptosis and accounts for about 5% of the single-hit killing measured by clonogenic assay. Temporal studies of radiation-induced killing of DU-145 cells distinguished this rapid mechanism of cell death from the major mechanism (72-144 h). These may correlate with apoptosis and proliferative cell death, respectively. Of the three prostate cancer cell lines investigated, only DU-145 cells displayed significant levels of radiation-induced DNA fragmentation and rapid cell death, with characteristics of apoptosis. This mechanism of cell death was complete by 24 h after irradiation and was well separated in time from the death of cells by the major mechanisms which occurred after 72 h, and accounted for about 5% of cell inactivation by a single-hit mechanism.

In the past 15 yrs, a number of investigators have applied spectral analysis to respiratory sounds recorded from the chest wall or the trachea in order to objectively characterize them and to relate them with different pulmonary diseases. In the present study, we have applied multivariate linear discriminant analysis to the spectral features of respiratory sounds. Lung sounds and the airflow velocity were recorded from 15 normal adults and 37 patients falling into three different disease categories: chronic obstructive lung disease, bronchial asthma and bronchiectasis. All patients had prominent adventitious lung sounds (i.e. either wheezes or crackles). Amplitude spectra of five selected inspiratory and expiratory sound segments of each subject were calculated using the Fast Fourier Transform algorithm. Multi-variate linear discriminant analysis was then applied to the normalized and averaged spectral area values calculated for 10 unequal and arbitrarily selected frequency bands for each patient in the frequency range between 80 Hz and 1 kHz. Inspiratory and expiratory sounds were treated separately. Discriminant functions were computed from the spectral area values and plotted on graphs to classify the subjects into one of the disease categories or as normal (training set). While some separation was achieved among the different disease groups, a clearer separation was evident between normals and patients as a whole on the basis both of inspiratory and expiratory sounds. Inspiratory and expiratory sound frequency bands having the largest weights in classification were determined. Admittedly, the specific results of this study are preliminary or even tentative in view of the inadequacies of sound recording and signal conditioning techniques that were available to us at the time of recording. However, we believe that the investigation serves to illustrate the potential of multivariate discriminant analysis in the diagnostic classification of patients on the basis of their lung sound patterns. We suggest that this technique be considered by investigators involved in lung sound research, because it also allows other patient variables to be combined with the selected parameters of lung sounds.

Four patients with intracranial neoplasms, two with malignant gliomas and two with brain metastases, were treated with stereotactic radiotherapy. Patients received between 15 and 27.5 Gray of photon irradiation to the central tumor target point; the 80% isodose line covered the periphery of the tumor as determined by contrast enhanced computed tomography. Patients underwent a sequence of three Positron Emission Tomographic scans using [18F]-fluorodeoxyglucose (PET-FDG)--a baseline scan the day before treatment, and follow-up scans 1 and 7 days after treatment. Ratios between the maximal tumor regional cerebral metabolic rate for glucose (rCMRGlu) (T*) and the contralateral remote white matter rCMRGlu (RW), that is, the glucose uptake ratio (T*/RW), were calculated. The percent change in ratios relative to each patient's baseline scan were calculated. Ratios increased 25% to 42% 1 day post-radiotherapy, then decreased to between 10% above and 12% below the baseline value 7 days post-radiotherapy. The T*/RW increased acutely after stereotactic radiotherapy in a fashion similar to that previously described following chemotherapy with a complex multi-drug regimen. A common metabolic pathway may underlie the increase in T*/RW after these different treatments.