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Background: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS)., Materials and Methods: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy., Results: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed., Conclusions: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety., (Copyright © 2021. Published by Elsevier Inc.)

The sparing of the parotid glands in the treatment of head and neck cancers is of clinical relevance as high doses to the salivary glands may result in xerostomia. Xerostomia is a major cause of decreased quality of life for head and neck patients. This paper explores the relationship between the overlap of the target volumes and their expansions with the parotid glands for helical delivery plans and their ability to be spared. Various overlapping volumes were examined, and an overlap with a high statistical relevance was found. A model that predicts exceeding tolerance parotid mean dose based on its fractional overlapping volume with PTVs was developed. A fractional overlapping volume of 0.083 between the parotid gland and the high dose PTV plus 5 mm expansion - was determined to be the threshold value to predict parotid D mean  > 26 Gy for parotids that overlap with the high dose PTV plus 5 mm expansion. If the parotid gland only overlaps with the intermediate dose target (and/or low dose target) and the overlapping volume of the parotid gland and the intermediate dose target is less than 25%, the parotid mean dose is likely less than 26 Gy. If the parotid overlaps with the low dose target only then the mean dose to the parotid is likely to be less than 26 Gy. This finding will prove as a very useful guide for the physicians and planners involved in the planning process to know prior whether the parotid glands will be able to be spared with the current set of target volumes or if revisions are necessary. This work will serve as a helpful guide in the planning process of head and neck target cases., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min -1 treatment delivery) is expected to generate an average 1000 photons per mm 2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2×  lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to  ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

Three-dimensional measurement arrays are an efficient means of acquiring a distribution of data for patient plan delivery QA. However, the tie between plan integrity and traditional gamma-based analysis of these data are not clear. This study explores the sensitivity of such analysis by creating errors in Helical Tomotherapy delivery and measuring the passing rates with an ArcCHECK cylindrical diode array. Errors were introduced in each of the couch speed, leaf open time, and gantry starting position in increasing magnitude while the resulting gamma passing rates were tabulated. The error size required to degrade the gamma passing rate to 90% or below was on average a 3% change in couch speed, 5° in gantry synchronization, or a 5 ms in leaf closing speed for a 3%/3 mm Van Dyk gamma analysis. This varied with plan type, with prostate plans exhibiting less sensitivity than head and neck plans and with gamma analysis criteria, but in all cases the error magnitudes were large compared to actual machine tolerances. These findings suggest that the sensitivity of ArcCHECK-based gamma analysis to single-mode errors in tomotherapy plans is dependent upon plan and analysis type and at traditional passing thresholds unable to detect small defects in the plan.

Purpose: Chemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location., Methods and Materials: Patients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk., Results: One hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence., Conclusions: Elective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer., Methods: Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program., Results: The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions., Conclusions: Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Treatment of locally advanced non-small cell lung cancer (LA-NSCLC) involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and resection, but radiation treatment volumes remain in question. With CRT, involved-field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing toxicity, and allowing dose escalation. However, prior reports of IFRT describe failures only after radical CRT; with improved local control after resection, IFRT may lead to more regional recurrences. Our objective is to evaluate pattern-of-failure in patients with LA-NSCLC treated with split-course IFRT, chemotherapy, and subsequent surgery., Methods and Materials: Patients treated between December 2004 and 2010 were included. Imaging scans demonstrating failure were fused into the radiation therapy planning computed tomography, and recurrent nodes were contoured to determine pattern-of-failure (involved versus elective nodal failure [INF vs ENF]). Locoregional progression-free survival and distant metastasis-free survival were calculated using Kaplan-Meier methodology. The cumulative incidence of regional recurrence (CIRR) was determined with death as a competing risk., Results: Forty-five patients met inclusion criteria, and patients with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With a median follow-up of 2.9 years, median survival was not reached, and 3-year locoregional progression-free survival and distant metastasis-free survival were 53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively. There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and 5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred without INF, both with distant metastasis, and no elective node was the first and only site of failure., Conclusions: Our data suggest that IFRT does not compromise regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal volumes may improve treatment-related morbidity and allow for dose intensification of involved nodes. Further research is necessary to improve regional and distant control., (Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: We compared integral dose with uninvolved brain (IDbrain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit., Methods: We prepared four PBRT treatment plans for four patients with high-grade gliomas (60 Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and IDbrain for all plans., Results: There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. IDbrain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean IDbrain 23.64 Gy vs. 28 Gy and 18.7 Gy vs. 24.5 Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7 Gy vs. 23.64 Gy and 24.5 Gy vs. 28 Gy, respectively)., Conclusions: In the setting of PBRT for high-grade gliomas, IMRT reduces IDbrain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces IDbrain compared with STD PBRT delivered with either traditional IMRT or HT., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Introduction: The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT)., Methods and Materials: Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BED(late effects)) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing)., Results: We were able to reduce physical dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6-66%, respectively., Conclusion: It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy., (© 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.)

Purpose: Supine tangential radiotherapy for the intact breast is a standard component of breast conservation management; a supraclavicular (SCV) field can be added for patients at high risk for nodal failure. Treatment in the prone position has demonstrated improvements in lung sparing, but has been limited to early-stage patients in whom radiation to only the breast was indicated. We sought to investigate the dosimetric feasibility of treating women in the prone position, using a 3-field monoisocentric technique., Methods: A total of 10 patients previously simulated supine and prone were selected for replanning. The heart, ipsilateral breast, contralateral breast, and axillary/SCV lymph node regions were contoured in accordance with Radiation Therapy Oncology Group guidelines. The 3-field monoisocentric plans were created for both the supine and prone scans. Target coverage, homogeneity, and organ at risk sparing were examined., Results: Both plans achieved acceptable coverage of the breast. The mean percentage of the breast receiving at least 95% of the prescription dose (V95%) were similar in the prone and supine positions, 89.3% versus 90.7% (P = 0.29). Mean V95% of the level 3 axilla and SCV were 93.8% versus 97.0% prone versus supine (P = 0.16). The percentage of ipsilateral lung receiving >20 Gy was substantially reduced from 21.2% supine to 9.3% prone (P = 0.001)., Conclusion: Three-field radiotherapy in the prone position appears to be dosimetrically equivalent to supine treatment with respect to target coverage, but the prone position decreases lung dose.

Purpose: To assess the feasibility of dosimetrically sparing the hippocampus and neural stem cell (NSC) compartment during whole-brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI)., Methods and Materials: We contoured the brain/brainstem on fused magnetic resonance /computed tomography images as the planning target volume (PTV) in 10 patients, excluding the hippocampus and NSC compartment as organs at risk. PCI and WBRT helical tomotherapy plans were prepared for each patient, with 1.0-cm field width, a pitch of 0.285, and a modulation factor of 2.5. We attempted to maximally spare the hippocampus and NSC compartment while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with a V(100) of ≥95%. Plan quality was assessed by calculating mean dose, equivalent uniform dose (EUD), and biologically equivalent dose (BED) for organs at risk and the percent volume of the PTV receiving the prescribed dose of V(100)., Results: In the PCI plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.5 Gy/13.1 Gy/15.7 Gy(2) (BED assuming alpha/beta ratio of 2Gy) and 11.5 Gy/13.1 Gy/12.3 Gy(10) (BED assuming alpha/beta ratio of 10Gy), respectively. In the WBRT plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.8 Gy/14.8 Gy/16.8 Gy(2) and 11.8 Gy/14.8 Gy/12.8 Gy(10), respectively. The mean V(95) for the rest of the brain (PTV) was 96.9% for both the PCI and WBRT plans. Mean PCI and WBRT treatment times were 15.93 min (range, 14.28 min-17.50 min) and 20.18 min (range, 18.43 min-22.32 min), respectively., Conclusions: It is dosimetrically feasible to spare the hippocampus and NSC compartment using helical tomotherapy during the administration of whole-brain irradiation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with "a" = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study., (2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

We present a case report of a patient recently treated at our institution for an isolated non-small cell lung cancer metastatic lesion to the sella, report the lack of involvement of the pituitary gland in a large single-institution series of treated intracranial parenchymal metastases, and review the pertinent literature. We reviewed cranial imaging studies (CT and MRI) for 935 metastases in 155 patients treated at our institution over the previous 3 years for intracranial metastatic disease. Special attention was paid to the skull base to document the presence of any metastatic disease involving the pituitary gland, infundibular stalk, sella turcica (including anterior and posterior clinoids), or diaphragm sellae. We found no other involvement of the pituitary gland or other sellar structures by metastatic disease in this series. Intracranial metastatic disease rarely involves the pituitary gland and infundibular stalk parenchyma, suggesting that this structure may be safely omitted from the treatment field during WBRT and prophylactic cranial irradiation (PCI). This treatment approach should reduce the late sequelae of treatment to this critical organ.

Introduction: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI)., Methods and Materials: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V(100) >or= 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V(100)., Results: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V(100) for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5)., Conclusions: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.

Background and Purpose: RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5mm margin)., Materials/methods: Patients with < or = 10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p<0.05 for statistical significance., Results: 1133 metastases were identified in 371 patients. Metastases within 5mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm(3) increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p=0.003) for the presence of perihippocampal metastasis., Conclusion: With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Patients with breast cancer are often treated with radiation to the breast (or chest wall) and draining regional lymph nodes. This is typically performed with a three-field technique in which an anterior supraclavicular field is matched to opposed tangent fields. A single isocenter technique is not always possible. Several techniques have been described to create a perfect match using a conventional simulator. We describe and test a simple, fast and accurate technique to estimate the couch and collimator angles required for a perfect geometric match using 3-D treatment planning software. This method requires no mathematical formulae and is verifiable relative to patient anatomy. An external skin contour is created on the axial slice at the match line and displayed with a 3-D representation. Using a beam's eye view (BEV) of a tangent field, small couch and collimator rotation adjustments are made sequentially until the contour edges are superimposed. The virtual external contour technique was easy to use, gave verification of the match in the BEV and yielded estimates of couch and collimator rotations very close to those calculated using published formulae.

Partial breast irradiation (PBI) was designed in part to decrease overall treatment times associated with whole breast radiation therapy (WBRT). WBRT treats the entire breast and usually portions of the axilla. The goal of PBI is to treat a smaller volume of breast tissue in less time, focusing the dose around the lumpectomy cavity. The following is a case of a 64-year-old woman with early-stage breast cancer treated with PBI who failed regionally in the ipsilateral axilla. With our dosimetric analysis, we found that the entire area of this axillary failure would have likely received at least 45 Gy if WBRT had been used, enough to sterilize microscopic disease. With PBI, this area received a mean dose of only 2.8 Gy, which raises the possibility that this regional failure may have been prevented had WBRT been used instead of PBI.

We report on the use of the EGS4/BEAM Monte Carlo technique to predict the output factors for clinically relevant, irregularly shaped inserts as they intercept a linear accelerator's electron beams. The output factor for a particular combination--energy, cone, insert, and source-to-surface distance (SSD)--is defined in accordance with AAPM TG-25 as the product of cone correction factor and insert correction factor, evaluated at the depth of maximum dose. Since cone correction factors are easily obtained, we focus our investigation on the insert correction factors (ICFs). An analysis of the inserts used in routine clinical practice resulted in the identification of a set of seven "idealized" shapes characterized by specific parameters. The ICFs for these shapes were calculated using a Monte Carlo method (EGS4/BEAM) and measured for a subset of them using an ion chamber and well-established measurement methods. Analytical models were developed to predict the Monte Carlo-calculated ICF values for various electron energies, cone sizes, shapes, and SSDs. The goodness-of-fit between predicted and Monte Carlo-calculated ICF values was tested using the Kolmogorov-Smirnoff statistical test. Results show that Monte Carlo-calculated ICFs match the measured values within 2.0% for most of the shapes considered, except for few highly elongated fields, where deviations up to 4.0% were recorded. Predicted values based on analytical modeling agree with measured ICF values within 2% to 3% for all configurations. We conclude that the predicted ICF values based on modeling of Monte Carlo-calculated values could be introduced in clinical use.

A technique was developed to reduce the size and magnitude of the hot and cold spots in the abutting regions of photon and electron fields. The photon and electron fields were set up such that the photon field extended approximately 2 cm into the electron field in the abutting region. The region of the photon beam that overlapped the electron field was modulated using a multileaf collimator, effectively broadening the photon penumbra to make it complimentary to the electron penumbra. The computer calculations were verified using film measurements for abutting a 6 MV photon beam with a 9 MeV electron beam. A uniform dose was achieved at a prespecified depth of 2 cm, and dose uniformity was improved at the specified depth and beyond compared with unmodulated photon beams. A slight increase in dose inhomogeneity was seen at shallower depths. The overall areas of the hot and cold spots were significantly reduced. The technique also reduced the sensitivity of dose homogeneity to setup errors such that the magnitudes of the hot and cold spots were about half of those produced with unmodulated photon beam when an overlap or gap of 4 mm was introduced. The technique was applied to the treatment of a head and neck cancer and a lymphoma involving the right pleura with markedly reduced dose inhomogeneity in the abutting regions.

Hematopoietic stem cell (HSC) self-renewal in vitro has been reported to result in a diminished proliferative capacity or acquisition of a homing defect that might compromise marrow repopulation. Our group has demonstrated that human HSC expanded ex vivo in the presence of porcine microvascular endothelial cells (PMVEC) retain the capacity to competitively repopulate human bone fragments implanted in severe combined immunodeficiency (SCID) mice. To further test the marrow repopulating capacity of expanded stem cells, our laboratory has established a myeloablative, fractionated total body irradiation conditioning protocol for autologous marrow transplantation in baboons. A control animal, which received no transplant, as well as two animals, which received a suboptimal number of marrow mononuclear cells, died 37, 43, and 59 days postirradiation, respectively. Immunomagnetically selected CD34(+) marrow cells from two baboons were placed in PMVEC coculture with exogenous human cytokines. After 10 days of expansion, the grafts represented a 14-fold to 22-fold increase in cell number, a 4-fold to 5-fold expansion of CD34(+) cells, a 3-fold to 4-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM), and a 12-fold to 17-fold increase of cobblestone area-forming cells (CAFC) over input. Both baboons became transfusion independent by day 23 posttransplant and achieved absolute neutrophil count (ANC) >500/microL by day 25 +/- 1 and platelets >20,000/microL by day 29 +/- 2. This hematopoietic recovery was delayed in comparison to two animals that received either a graft consisting of freshly isolated, unexpanded CD34(+) cells or 175 x 10(6)/kg unfractionated marrow mononuclear cells. Analysis of the proliferative status of cells in PMVEC expansion cultures demonstrated that by 10 days, 99.8% of CD34(+) cells present in the cultures had undergone cycling, and that the population of cells expressing a CD34(+) CD38(-) phenotype in the cultures was also the result of active cell division. These data indicate that isolated bone marrow CD34(+) cells may undergo cell division during ex vivo expansion in the presence of endothelial cells to provide a graft capable of rescuing a myeloablated autologous host.

The optimal field shape achieved using a multileaf collimator (MLC) often requires collimator rotation to minimize the adverse effects of the scalloped dose distribution the leaf steps produce. However, treatment machines are designed to deliver wedged fields parallel or perpendicular to the direction of the leaves. An analysis of cases from our clinic showed that for 25% of the wedged fields used to treat brain and lung tumors, the wedge direction and optimal MLC orientation differed by 20 degrees or more. The recently published omni wedge technique provides the capability of producing a wedged field with orientation independent of the orientation of the collimator. This paper presents a comparison of the three-dimensional (3D) dose distributions of the omni wedged field with distributions of wedged fields produced using both the universal and dynamic wedge techniques. All measurements were performed using film dosimetry techniques. The omni wedge generated fields closely matched the conventional wedged fields. Throughout 95% of the irradiated volume (excluding the penubra), the dose distribution of the omni wedged field ranged from +5.5 to -3.5 +/- 1.5% of that of the conventionally wedged fields. Calculation of the omni wedged field is as accurate as conventional wedged field calculation when using a 3D treatment planning systems. For two-dimensional treatment planning systems, where one must assume that the omni wedged field is identical to a conventional field, the calculated field and the delivered field differs by a small amount.