Publications by authors named "Kenneth M Forster"

27 Publications

  • Page 1 of 1

Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

Front Oncol 2020 9;10:591430. Epub 2021 Feb 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking . compression or gating).

Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator.

Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range.

Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.
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http://dx.doi.org/10.3389/fonc.2020.591430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900559PMC
February 2021

Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer.

Int J Radiat Oncol Biol Phys 2020 Dec 24. Epub 2020 Dec 24.

Department of Radiation Oncology, Northwell Health, New York, New York.

Purpose: Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa.

Methods And Materials: A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting.

Results: After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%.

Conclusions: Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.017DOI Listing
December 2020

Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer.

J Clin Oncol 2020 03 16;38(7):706-714. Epub 2019 Dec 16.

The University of Texas Southwestern Medical Center, Dallas, TX.

Purpose: RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer (NSCLC).

Methods: The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS).

Results: Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm 12.1% and 17.4% in the HD arm, respectively ( = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 20.3 months ( = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms.

Conclusion: A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
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http://dx.doi.org/10.1200/JCO.19.01162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048161PMC
March 2020

Dependence of ventilation image derived from 4D CT on deformable image registration and ventilation algorithms.

J Appl Clin Med Phys 2013 Jul 8;14(4):4247. Epub 2013 Jul 8.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.

Ventilation imaging using 4D CT is a convenient and low-cost functional imaging methodology which might be of value in radiotherapy treatment planning to spare functional lung volumes. Deformable image registration (DIR) is needed to calculate ventilation imaging from 4D CT. This study investigates the dependence of calculated ventilation on DIR methods and ventilation algorithms. DIR of the normal end expiration and normal end inspiration phases of the 4D CT images was used to correlate the voxels between the two respiratory phases. Three different DIR algorithms, optical flow (OF), diffeomorphic demons (DD), and diffeomorphic morphons (DM) were retrospectively applied to ten esophagus and ten lung cancer cases with 4D CT image sets that encompassed the entire lung volume. The three ventilation extraction methods were used based on either the Jacobian, the change in volume of the voxel, or directly calculated from Hounsfield units. The ventilation calculation algorithms used are the Jacobian, ΔV, and HU method. They were compared using the Dice similarity coefficient (DSC) index and Bland-Altman plots. Dependence of ventilation images on the DIR was greater for the ΔV and the Jacobian methods than for the HU method. The DSC index for 20% of low-ventilation volume for ΔV was 0.33 ± 0.03 (1 SD) between OF and DM, 0.44 ± 0.05 between OF and DD, and 0.51 ± 0.04 between DM and DD. The similarity comparisons for Jacobian were 0.32 ± 0.03, 0.44 ± 0.05, and 0.51 ± 0.04, respectively, and for HU they were 0.53 ± 0.03, 0.56 ± 0.03, and 0.76 ± 0.04, respectively. Dependence of extracted ventilation on the ventilation algorithm used showed good agreement between the ΔV and Jacobian methods, but differed significantly for the HU method. DSC index for using OF as DIR was 0.86 ± 0.01 between ΔV and Jacobian, 0.28 ± 0.04 between ΔV and HU, and 0.28 ± 0.04 between Jacobian and HU, respectively. When using DM or DD as DIR, similar values were obtained when comparing the different ventilation calculation methods. The similarity values for the 20% high-ventilation volume were close to those found for the 20% low-ventilation volume. The results obtained with DSC index were confirmed when using the Bland-Altman plots for comparing the ventilation images. Our data suggest that ventilation calculated from 4D CT depends on the DIR algorithm employed. Similarities between ΔV and Jacobian are higher than between ΔV and HU, and Jacobian and HU.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714535PMC
http://dx.doi.org/10.1120/jacmp.v14i4.4247DOI Listing
July 2013

Providing a fast conversion of total dose to biological effective dose (BED) for hybrid seed brachytherapy.

J Appl Clin Med Phys 2012 Sep 6;13(5):3800. Epub 2012 Sep 6.

Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.

Optimization of permanent seed implant brachytherapy plans for treatment of prostate cancer should be based on biological effective dose (BED) distributions, since dose does not accurately represent biological effects between different types of sources. Currently, biological optimization for these plans is not feasible due to the amount of time necessary to calculate the BED distribution. This study provides a fast calculation method, based on the total dose, to calculate the BED distribution. Distributions of various numbers of hybrid seeds were used to calculate total dose distributions, as well as BED distributions. Hybrid seeds are a mixture of different isotopes (in this study (125)I and (103)Pd). Three ratios of hybrid seeds were investigated: 25/75, 50/50, and 75/25. The total dose and BED value from each voxel were coupled together to produce graphs of total dose vs. BED. Equations were then derived from these graphs. The study investigated four types of tissue: bladder, rectum, prostate, and other normal tissue. Equations were derived from the total dose - BED correspondence. Accuracy of conversion from total dose to BED was within 2 Gy; however, accuracy of conversion was found to be better for high total dose regions as compared to lower dose regions. The method introduced in this paper allows one to perform fast conversion of total dose to BED for brachytherapy using hybrid seeds, which makes the BED-based plan optimization practical. The method defined here can be extended to other ratios, as well as other tissues that are affected by permanent seed implant brachytherapy (i.e., breast).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718217PMC
http://dx.doi.org/10.1120/jacmp.v13i5.3800DOI Listing
September 2012

Promise and pitfalls of quantitative imaging in oncology clinical trials.

Magn Reson Imaging 2012 Nov 13;30(9):1301-12. Epub 2012 Aug 13.

Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.

Quantitative imaging using computed tomography, magnetic resonance imaging and positron emission tomography modalities will play an increasingly important role in the design of oncology trials addressing molecularly targeted, personalized therapies. The advent of molecularly targeted therapies, exemplified by antiangiogenic drugs, creates new complexities in the assessment of response. The Quantitative Imaging Network addresses the need for imaging modalities which can accurately and reproducibly measure not just change in tumor size but changes in relevant metabolic parameters, modulation of relevant signaling pathways, drug delivery to tumor and differentiation of apoptotic cell death from other changes in tumor volume. This article provides an overview of the applications of quantitative imaging to phase 0 through phase 3 oncology trials. We describe the use of a range of quantitative imaging modalities in specific tumor types including malignant gliomas, lung cancer, head and neck cancer, lymphoma, breast cancer, prostate cancer and sarcoma. In the concluding section, we discuss potential constraints on clinical trials using quantitative imaging, including complexity of trial conduct, impact on subject recruitment, incremental costs and institutional barriers. Strategies for overcoming these constraints are presented.
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http://dx.doi.org/10.1016/j.mri.2012.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466405PMC
November 2012

Calculating prescription doses for new sources by biologically effective dose matching.

Brachytherapy 2012 Nov-Dec;11(6):521-7. Epub 2012 Mar 19.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.

Purpose: In current clinical practice, single isotopes, such as (125)I or (103)Pd, are used as single sources in prostate seed implants. A mixture of two radionuclides in the seeds has been proposed for prostate cancer treatment. This study investigates a method for determining the prescription dose for these new seeds using the biological effective dose (BED).

Methods: Ten prostate cancer cases previously treated using single radionuclide seeds were selected for this study. The BED distribution for these cases was calculated. Plans using other radionuclides were then calculated based on this BED distribution. Prescription values could then be obtained for the calculated plans. The method was verified by calculating the prescription dose for (103)Pd and (125)I and comparing to clinical values. The method was then applied to a hybrid seed that consisted of a mixture of (125)I and (103)Pd radionuclides, which deliver equal dose to 1cm from the source in water (50/50D@1 cm). A prescription BED value was also calculated.

Results: A prescription BED of 110 Gy was found to correlate to a prescription dose of 145, 120, and 137 Gy for (125)I, (103)Pd, and 50/50D@1 cm hybrid seeds, respectively.

Conclusion: The method introduced in this article allows one to calculate the prescription dose for new and novel sources in brachytherapy. The method was verified by calculating a prescription dose for (125)I and (103)Pd radionuclides that coincides with values used clinically.
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http://dx.doi.org/10.1016/j.brachy.2012.02.003DOI Listing
May 2013

Validating fiducial markers for image-guided radiation therapy for accelerated partial breast irradiation in early-stage breast cancer.

Int J Radiat Oncol Biol Phys 2012 Mar;82(3):e425-31

Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Purpose: Image-guided radiation therapy (IGRT) may be beneficial for accelerated partial breast irradiation (APBI). The goal was to validate the use of intraparenchymal textured gold fiducials in patients receiving APBI.

Methods And Materials: Twenty-six patients were enrolled on this prospective study that had three or four textured gold intraparenchymal fiducials placed at the periphery of the lumpectomy cavity and were treated with three-dimensional (3D) conformal APBI. Free-breathing four-dimensional computed tomography image sets were obtained pre- and posttreatment, as were daily online megavoltage (MV) orthogonal images. Intrafraction motion, variations in respiratory motion, and fiducial marker migration were calculated using the 3D coordinates of individual fiducials and a calculated center of mass (COM) of the fiducials. We also compared the relative position of the fiducial COM with the geometric center of the seroma.

Results: There was less than 1 mm of intrafraction respiratory motion, variation in respiratory motion, or fiducial marker migration. The change in seroma position relative to the fiducial COM was 1 mm ± 1 mm. The average position of the geometric seroma relative to the fiducial COM pretreatment compared with posttreatment was 1 mm ± 1 mm. The largest daily variation in displacement when using bony landmark was in the anteroposterior direction and two standard deviations (SD) of this variation was 10 mm. The average variation in daily separation between the fiducial pairs from daily MV images was 3 mm ± 3 mm therefore 2 SD is 6 mm.

Conclusion: Fiducial markers are stable throughout the course of APBI. Planning target volume margins when using bony landmarks should be 10 mm and can be reduced to 6 mm if using fiducials.
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http://dx.doi.org/10.1016/j.ijrobp.2011.07.027DOI Listing
March 2012

Compensator-based intensity-modulated radiation therapy for malignant pleural mesothelioma post extrapleural pneumonectomy.

J Appl Clin Med Phys 2008 Oct 29;9(4):98-109. Epub 2008 Oct 29.

H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, Florida, U.S.A.

The present work investigated the potential of compensator-based intensity-modulated radiation therapy (CB-IMRT) as an alternative to multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) to treat malignant pleural mesothelioma (MPM) post extrapleural pneumonectomy. Treatment plans for 4 right-sided and 1 left-sided MPM post-surgery cases were generated using a commercial treatment planning system, XIO/CMS (Computerized Medical Systems, St. Louis, MO). We used a 7-gantry-angle arrangement with 6 MV beams to generate these plans. The maximum required field size was 30 x 40 cm. We evaluated IMRT plans with brass compensators (.Decimal, Sanford, FL) by examining isodose distributions, dose-volume histograms, metrics to quantify conformal plan quality, and homogeneity. Quality assurance was performed for one of the compensator plans. Conformal dose distributions were achieved with CB-IMRT for all 5 cases, the average planning target volume (PTV) coverage being 95.1% of the PTV volume receiving the full prescription dose. The average lung V20 (volume of lung receiving 20 Gy) was 1.8%, the mean lung dose was 6.7 Gy, and the average contralateral kidney V15 was 0.6%. The average liver dose V30 was 34.0% for the right-sided cases and 10% for the left-sided case. The average monitor units (MUs) per fraction were 980 MUs for the 45-Gy prescriptions (mean: 50 Gy) and 1083 MUs for the 50-Gy prescriptions (mean: 54 Gy). Post surgery, CB-IMRT for MPM is a feasible IMRT technique for treatment with a single isocenter. Compensator plans achieved dose objectives and were safely delivered on a Siemens Oncor machine (Siemens Medical Solutions, Malvern, PA). These plans showed acceptably conformal dose distributions as confirmed by multiple measurement techniques. Not all linear accelerators can deliver large-field MLC-based IMRT, but most can deliver a maximum conformal field of 40 x 40 cm. It is possible and reasonable to deliver IMRT with compensators for fields this size with most conventional linear accelerators.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722359PMC
http://dx.doi.org/10.1120/jacmp.v9i4.2799DOI Listing
October 2008

Functional lung imaging in thoracic cancer radiotherapy.

Cancer Control 2008 Apr;15(2):112-9

Radiation Oncology Program at the Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Background: Lung cancer is the No. 1 cancer killer of both men and women in the United States. Radiotherapy is frequently employed as part of the treatment. However, radiation must traverse surrounding regions of normal lung, potentially inducing pulmonary toxicity. Because these patients frequently have underlying lung disease, a radiation-induced decrement in lung function could be highly morbid or even fatal. It is well known that lung function is not uniform, with wide ranges of ventilation and perfusion levels throughout the lung. Currently radiation oncologists do not have the ability to account for this variation when generating treatment plans.

Methods: This article reviews some techniques used to assess pulmonary ventilation and perfusion, including nuclear medicine, magnetic resonance imaging (MRI) and computed tomography (CT).

Results: Many techniques have the potential to be used in radiotherapy treatment planning for thoracic cancer patients to spare normal functional lung volumes while delivering adequate radiation dose to the tumors. The article outlines a promising new technique to generate 3-D ventilation maps by using deformable image registration of 4-D CT image sets.

Conclusions: While there are some technical challenges to overcome before pulmonary functional imaging can be routinely employed clinically in radiation oncology, there is the potential to preferentially spare better perfused/ventilated regions of normal lung, which promises to reduce pulmonary toxicity.
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http://dx.doi.org/10.1177/107327480801500203DOI Listing
April 2008

Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma.

Ann Thorac Surg 2007 Nov;84(5):1685-92; discussion 1692-3

Department of Thoracic and Cardiovascular Surgery, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.

Background: Malignant pleural mesothelioma is a locally aggressive tumor that is usually fatal. Extrapleural pneumonectomy (EPP) followed by hemithoracic irradiation has shown promise, but local failure remains a significant problem. To improve local control, we have used intensity-modulated radiation therapy (IMRT) as it allows better dose distribution to regions at risk of recurrence as well as reduced radiation to surrounding organs.

Methods: One hundred consecutive patients underwent EPP. At a median interval of 2.5 months from surgery, 63 patients received IMRT (median dose 45 Gy) with curative intent. Chemotherapy was not routinely administered.

Results: Tumors were right sided in 66 patients (66%) and nonepithelioid in 33 (33%). American Joint Committee on Cancer pathology stage was I in 6 patients (6%), II in 7 (7%), III in 72 (72%), and IV (T4) in 15 (15%). Fifty-four patients (54%) had ipsilateral nodal metastases. Perioperative mortality was 8%. Median overall survival (n = 100) was 10.2 months. For patients who received IMRT (n = 63), median overall and 3-year survival was 14.2 months and 20%. Of these, node-negative patients with epithelioid histology (n = 18) had median and 3-year survival of 28 months and 41%. Distant recurrences occurred in 33 of 61 evaluable patients (54%). Eight patients (13%) had local or regional recurrence, 5 of whom also recurred distally. Only 3 patients (5%) had recurrence within the irradiated field.

Conclusions: Intensity-modulated radiation therapy after EPP results in excellent local control for malignant pleural mesothelioma; however, distant metastases remain a significant problem and limit survival. This provides a strong rationale for combining aggressive local regimens with systemic therapy.
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http://dx.doi.org/10.1016/j.athoracsur.2007.04.076DOI Listing
November 2007

Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma.

Int J Radiat Oncol Biol Phys 2007 Oct 30;69(2):350-7. Epub 2007 Apr 30.

Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Purpose: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma.

Methods And Materials: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at the University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non-cancer-related death within 6 months of IMRT.

Results: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving >or=20 Gy (V(20); p = 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V20 was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08-2.08) or non-cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02-1.45).

Conclusion: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V20 was the only independent determinant for risk of PRD or non-cancer-related death. The mean V20 of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V20 should be kept as low as possible after extrapleural pneumonectomy.
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http://dx.doi.org/10.1016/j.ijrobp.2007.03.011DOI Listing
October 2007

The management of respiratory motion in radiation oncology report of AAPM Task Group 76.

Med Phys 2006 Oct;33(10):3874-900

Virginia Commonwealth University, USA.

This document is the report of a task group of the AAPM and has been prepared primarily to advise medical physicists involved in the external-beam radiation therapy of patients with thoracic, abdominal, and pelvic tumors affected by respiratory motion. This report describes the magnitude of respiratory motion, discusses radiotherapy specific problems caused by respiratory motion, explains techniques that explicitly manage respiratory motion during radiotherapy and gives recommendations in the application of these techniques for patient care, including quality assurance (QA) guidelines for these devices and their use with conformal and intensity modulated radiotherapy. The technologies covered by this report are motion-encompassing methods, respiratory gated techniques, breath-hold techniques, forced shallow-breathing methods, and respiration-synchronized techniques. The main outcome of this report is a clinical process guide for managing respiratory motion. Included in this guide is the recommendation that tumor motion should be measured (when possible) for each patient for whom respiratory motion is a concern. If target motion is greater than 5 mm, a method of respiratory motion management is available, and if the patient can tolerate the procedure, respiratory motion management technology is appropriate. Respiratory motion management is also appropriate when the procedure will increase normal tissue sparing. Respiratory motion management involves further resources, education and the development of and adherence to QA procedures.
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http://dx.doi.org/10.1118/1.2349696DOI Listing
October 2006

Radiotherapy for mesothelioma.

Hematol Oncol Clin North Am 2005 Dec;19(6):1099-115, vii

Division of Radiation Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.

Three to four thousand cases of malignant pleural mesothelioma will occur in the United States this year. Single-modality therapy with radiation plays a role for palliation. Radiation can prevent tumor recurrence at drain/instrumentation sites and provide symptomatic relief of pain and other complaints. Combinations of surgery and radiation also have been attempted with curative intent. The best local control has been found--EPP followed by radiotherapy. Locoregional tumor recurrence can be dramatically reduced with combinations of extrapleural pneumonectomy and radiation therapy. Survival in aggressively treated early-stage patients is excellent. However, the preponderance of death from distant metastases makes the development of better systemic therapy essential. Better therapy also must be developed for patients who are not candidates for extrapleural pneumonectomy.
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http://dx.doi.org/10.1016/j.hoc.2005.09.006DOI Listing
December 2005

Extracranial stereotactic radiation delivery.

Semin Radiat Oncol 2005 Jul;15(3):202-7

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas 75390-9183, USA.

Extracranial stereotactic radiation delivery, also known as stereotactic body radiation therapy (SBRT), involves delivering very potent doses of radiation to well-demarcated tumors in the neck, spine, chest, abdomen, and pelvis. Beyond just stereotactic targeting, it represents a formalism of treatment planning and conduct that facilitates the delivery of the most potent dose fractionation schedules ever considered in the field of radiation oncology. In doing so, it uses the most modern technologies to simultaneously hit the target and avoid normal innocent tissues. Clinical results already show that SBRT constitutes a new paradigm in cancer treatment that deserves careful implementation and assessment for the improvement in patient outcomes.
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http://dx.doi.org/10.1016/j.semradonc.2005.01.006DOI Listing
July 2005

Radiation injury to the liver after intensity-modulated radiation therapy in patients with mesothelioma: an unusual CT appearance.

AJR Am J Roentgenol 2005 Apr;184(4):1091-5

Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Box 57, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Objective: We sought to report the unusual distribution of radiation-induced injury to the liver in patients with mesothelioma after extrapleural pneumonectomy and intensity-modulated radiation therapy (IMRT).

Conclusion: Abnormal hepatic enhancement after extrapleural pneumonectomy and IMRT is common in patients with mesothelioma. Knowledge of the early occurrence and typical location and appearance of IMRT-induced injury can be useful in preventing misinterpretation as metastatic disease or recurrent tumor.
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http://dx.doi.org/10.2214/ajr.184.4.01841091DOI Listing
April 2005

Quality assurance evaluation of delivery of respiratory-gated treatments.

J Appl Clin Med Phys 2004 1;5(3):55-61. Epub 2004 Jul 1.

Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

We describe a method for evaluating the quality of respiratory-gated radiation delivery using a commercially available device. During irradiation, gating traces for one field for each treatment were extracted from the system for each of 14 patients. The data were then transferred to a spreadsheet. Software was developed to evaluate the following parameters: duty cycle, amplitude of fiducial motion, fraction of amplitude of motion during gated delivery, and respiratory cycle time. Criteria were established for acceptability of gating traces. In our sample, over 85% of the traces indicated acceptability. An example of results for one patient extracted from analyzed gating traces is as follows: mean duty cycle, 57%, average amplitude of motion, 0.89 cm, average fraction of motion during gated delivery, 0.45; mean respiratory cycle time, 4.5 s. This technique can be used to evaluate delivery of respiratory-gated radiation therapy for quality assurance purposes and to assess various techniques for improving delivery of gated therapy. A hardcopy of the gating traces can be used to document gated treatment delivery for potential billing of the gated delivery process.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723481PMC
http://dx.doi.org/10.1120/jacmp.v5i3.2002DOI Listing
March 2006

Dosimetric benefits of respiratory gating: a preliminary study.

J Appl Clin Med Phys 2004 1;5(1):16-24. Epub 2004 Jan 1.

Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

In this study, we compared the amount of lung tissue irradiated when respiratory gating was imposed during expiration with the amount of lung tissue irradiated when gating was imposed during inspiration. Our hypothesis was that the amount of lung tissue spared increased as inspiration increased. Computed tomography (CT) image data sets were acquired for 10 patients who had been diagnosed with primary bronchogenic carcinoma. Data sets were acquired during free breathing and during breath-holds at 0% tidal volume and 100% tidal volume, and, when possible, at deep inspiration, corresponding to approximately 60% vital capacity. Two treatment plans were developed on the basis of each of the gated data sets: one in which the treatment portals were those of the free-breathing plan, and the other in which the treatment portals were based on the gated planning target volumes. Dose-mass histograms of the lungs calculated at 0% tidal volume were compared to those calculated at deep inspiration and at 100% tidal volume. Data extracted from the dose-mass histograms were used to determine the most dosimetrically beneficial point to gate, the reduction in the amount of irradiated lung tissue that resulted from gating, and any disease characteristics that might predict a greater need for gating. The data showed a reduction in the mass of normal tissue irradiated when treatment portals based on the gated planning target volume were used. More normal lung tissue was spared at deep inspiration than at the other two gating points for all patients, but normal lung tissue was spared at every point in the respiratory cycle. No significant differences in the amount of irradiated tissue by disease characteristic were identified. Respiratory gating of thoracic radiation treatments can often improve the quality of the treatment plan, but it may not be possible to determine which patients may benefit from gating prior to performing the actual treatment planning.
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http://dx.doi.org/10.1120/jacmp.26.146DOI Listing
March 2006

Correlation of gross tumor volume excursion with potential benefits of respiratory gating.

Int J Radiat Oncol Biol Phys 2004 Nov;60(4):1291-7

Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.

Purpose: To test the hypothesis that the magnitude of thoracic tumor motion can be used to determine the desirability of respiratory gating.

Methods And Materials: Twenty patients to be treated for lung tumors had computed tomography image data sets acquired under assisted breath hold at normal inspiration (100% tidal volume), at full expiration (0% tidal volume), and under free breathing. A radiation oncologist outlined gross tumor volumes (GTVs) on the breath-hold computed tomographic images. These data sets were registered to the free-breathing image data set. Two sets of treatment plans were generated: one based on an internal target volume explicitly formed from assessment of the excursion of the clinical target volume (CTV) through the respiratory cycle, representing an ungated treatment, and the other based on the 0% tidal volume CTV, representing a gated treatment with little margin for residual motion. Dose-volume statistics were correlated to the magnitude of the motion of the center of the GTV during respiration.

Results: Patients whose GTVs were >100 cm(3) showed little decrease in lung dose under gating. The other patients showed a correlation between the excursion of the center of the GTV and a reduction in potential lung toxicity. As residual motion increased, the benefits of respiratory gating increased.

Conclusion: Gating seems to be advantageous for patients whose GTVs are <100 cm(3) and for whom the center of the GTV exhibits significant motion, provided residual motion under gating is kept small.
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http://dx.doi.org/10.1016/j.ijrobp.2004.07.707DOI Listing
November 2004

Promising early local control of malignant pleural mesothelioma following postoperative intensity modulated radiotherapy (IMRT) to the chest.

Cancer J 2003 Nov-Dec;9(6):476-84

Department of Radiation Oncology, Section of Thoracic Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Purpose: Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleural pneumonectomy and conventional radiotherapy. This may be due to failure to recognize the extent of clinical target volume (CTV) or suboptimal dose delivery to a target that abuts the heart, esophagus, liver, lung, kidney, and spinal cord. We report how these geometric/dosimetric constraints were overcome by exploiting intensity-modulated radiotherapy in the first cohort patient.

Materials And Methods: Twenty-eight patients who had undergone extrapleural pneumonectomy were treated with intensity-modulated radiotherapy. The CTV included the surgically violated inner chest wall, insertion of diaphragm, pleural reflections, and deep margin of the incision. CTV delineation was facilitated by intraoperative radio-opaque marking. Motion was assessed. CTV doses were 45-50 Gy with boosts taken to 60 Gy.

Results: Despite the large, irregular CTV (median, 4151 cc; range, 2667-7286 cc), an average of 97% of the CTV was covered to the target dose (range, 92%-100%). Respiratory motion was minimal because of immobility of the prosthetic diaphragm. Normal tissue dose constraints were met. The commonest effects were nausea/vomiting (89%) and dyspnea (80%). Esophagitis was absent (59% of patients) or mild (34% grade 1/2). At median follow-up of 9 months (range, 5-27 months), local control within the contoured target was 100%. One-year survival, disease-specific survival, and disease-free survival are 65%, 91%, and 88%, respectively.

Conclusions: Intensity-modulated radiotherapy after extrapleural pneumonectomy is tolerable and seems effective, at least at this early point. As local control improves, systemic metastases become more common, and it may be appropriate to add novel agents to further improve the therapeutic ratio.
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http://dx.doi.org/10.1097/00130404-200311000-00008DOI Listing
April 2004

Treatment planning for lung cancer: traditional homogeneous point-dose prescription compared with heterogeneity-corrected dose-volume prescription.

Int J Radiat Oncol Biol Phys 2003 Aug;56(5):1308-18

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Purpose: To quantify the differences in doses to target volumes and critical thoracic structures calculated by traditional homogeneous point-dose prescription and heterogeneity-corrected volume-dose prescription.

Methods And Materials: Between 1998 and 2001, 30 patients with inoperable Stage I/II non-small-cell lung cancer underwent radiation treatment planning at our institution. A commercially available convolution/superposition- based algorithm was used. Three treatment plans were calculated for each patient using identical beam geometries: one plan was generated by traditional homogeneous point-dose prescription, a second by the traditional method with heterogeneity correction, and a third by heterogeneity-corrected volume-dose prescription that would cover 95% of the planned target volume (PTV). Target volume coverage, isocenter dose, and dose uniformity in the second and third plans were compared.

Results: The PTV, clinical target volume (CTV), and isocenter calculated by the heterogeneity-corrected volume-dose method were equivalent to those calculated by the traditional homogeneous point-dose method with heterogeneity correction. The fraction of the PTV covered by heterogeneity-corrected volume-dose prescription was significantly greater than the fraction covered by traditional homogeneous point-dose prescription with heterogeneity correction (p = 0.05). The dose prescribed using the traditional method would have been delivered to less than 90% of the PTV in 14 of 30 patients. There was no significant difference in the maximum and minimum doses to the PTV, the CTV, or the isocenter calculated by the traditional homogeneous method with heterogeneity correction and the heterogeneity-corrected volume-dose method. There was also no significant difference in the planned volume of lung receiving greater than 20 Gy as calculated by these two methods.

Conclusion: When compared with traditional homogeneous radiation treatment planning, heterogeneity-corrected methods produce equivalent PTV, CTV, and isocenter doses while providing superior PTV coverage.
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http://dx.doi.org/10.1016/s0360-3016(03)00337-7DOI Listing
August 2003

Verification techniques and dose distribution for computed tomographic planned supine craniospinal radiation therapy.

Med Dosim 2003 ;28(2):127-31

Division of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.

A modified 3-field technique was designed with opposed cranial fields and a single spinal field encompassing the entire spinal axis. Two methods of plan verifications were performed before the first treatment. First, a system of orthogonal rulers plus the thermoplastic head holder was used to visualize the light fields at the craniospinal junction. Second, film phantom measurements were taken to visualize the gap between the fields at the level of the spinal cord. Treatment verification entailed use of a posterior-anterior (PA) portal film and placement of radiopaque wire on the inferior border of the cranial field. More rigorous verification required a custom-fabricated orthogonal film holder. The isocenter positions of both fields when they matched were recorded using a record-and-verify system. A single extended distance spinal field collimated at 42 degrees encompassed the entire spinal neuraxis. Data were collected from 40 fractions of craniospinal irradiation (CSI). The systematic error observed for the actual daily treatments was -0.5 mm (underlap), while the stochastic error was represented by a standard deviation of 5.39 mm. Measured data across the gapped craniospinal junction with junction shifts included revealed a dose ranging from 89.3% to 108%. CSI can be performed without direct visualization of the craniospinal junction by using the verification methods described. While the use of rigorous film verification for supine technique may have reduced the systematic error, the inability to visualize the supine craniospinal junction on skin appears to have increased the stochastic error compared to published data on such errors associated with prone craniospinal irradiation.
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http://dx.doi.org/10.1016/S0958-3947(02)00248-0DOI Listing
December 2003

The relationship between local dose and loss of function for irradiated lung.

Int J Radiat Oncol Biol Phys 2003 May;56(1):106-13

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Purpose: To determine the relationship between the local radiation dose and the decrease in lung function associated with thoracic irradiation.

Patients And Methods: Twenty-six patients treated with thoracic irradiation for lung cancer, for whom three-dimensional CT-based dosimetry was used in treatment planning, were evaluated with before and after treatment pulmonary function tests. Six patients were treated with radiotherapy alone (2.15 Gy daily fractions), and 20 patients with concurrent chemotherapy (cisplatin, etoposide) with hyperfractionated (HF) radiation therapy (1.2 Gy in twice-daily fractions). Eleven patients treated with concurrent HF chemoradiation also received the radioprotector amifostine. The normalized decrease in the diffusing capacity for carbon monoxide (DL(CO)) was used as an objective measure of the change in lung function. The dose-volume histogram (DVH) data were used to estimate the local dose-response relationship for loss of DL(CO). In each subvolume of lung, the loss in normalized DL(CO) was assumed to be a sigmoid function of dose, ranging from no loss at low doses to total loss at high doses. The whole-lung decrease in DL(CO) was modeled as the sum of the local declines in DL(CO) over all subvolumes. Nonlinear regression analysis was used to estimate the parameters of the local dose-response function.

Results: The data are most consistent with a pronounced decrease in DL(CO) when the local dose (for radiotherapy alone or HF concurrent chemoradiation) exceeds 13 Gy (95% CI, 11-15 Gy). In patients who received amifostine in addition to HF radiotherapy with concurrent chemotherapy, this stepwise loss of DL(CO) occurred above 36 Gy (95% CI, 25-48 Gy). Grade 2 or higher pulmonary symptoms were associated with a DL(CO) loss of >30% (p = 0.003).

Conclusions: The decrease in pulmonary diffusion capacity correlates with the local dose to irradiated lung. Amifostine significantly reduces the loss in DL(CO). A local dose-loss relationship for normalized DL(CO) can be extracted from DVH data. This relationship allows an estimate of the loss of function associated with a radiation treatment plan. Different plans can thus be compared without resort to an empiric DVH reduction algorithm. The very low (13 Gy) threshold for deterioration of DL(CO) suggests that it is better to treat a little normal lung to a high dose than to treat a lot to a low dose.
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http://dx.doi.org/10.1016/s0360-3016(03)00094-4DOI Listing
May 2003

Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma.

Int J Radiat Oncol Biol Phys 2003 Mar;55(3):768-75

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Purpose: Malignant pleural mesothelioma (MPM) causes symptoms and death mainly due to local progression, even after combined modality treatment. Poor local control after conventional radiotherapy may be due to the low dose of radiation that has been administered or to restriction of the target volume to avoid critical organs. Intensity-modulated radiation therapy (IMRT) has the potential to overcome these geometric/dosimetric constraints.

Methods And Materials: Seven patients with MPM who had an extrapleural pneumonectomy (EPP) were treated with adjuvant IMRT. The clinical target volume (CTV) included the surgically violated area inside the chest wall with particular attention to the insertion of the diaphragm, pleural reflections, and the deep margin of the thoracotomy incision. Treatment was delivered by intensity-modulated 6-MV photon beams using dynamic multileaf collimation.

Results: The CTV ranged from 2667 to 7286 mL. The average CTV covered to 50 Gy was 94% (range, 92% to 98%). Respiratory motion was minimal. The average volume of the boost areas covered by 60 Gy was 92% (range, 82% to 99%). Dose-volume constraints for normal tissue were met in almost all cases. Acute toxicity was mild to moderate. The most severe side effects were anorexia, nausea or vomiting, and dyspnea. Esophagitis was absent or mild. After a minimum of 13 months follow-up care there were no cases of disease recurrence within the ipsilateral hemithorax.

Conclusion: Treatment of the extensive operative area after an EPP is feasible using IMRT. Input from the radiologist and from the surgeon in the planning process facilitates definition of the high dose volumes. In light of patients' tolerance to post-EPP IMRT, it may be feasible to incorporate systemic therapy, including novel biologic therapies into the treatment regimen.
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http://dx.doi.org/10.1016/s0360-3016(02)04151-2DOI Listing
March 2003

Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation.

Int J Radiat Oncol Biol Phys 2003 Mar;55(3):606-16

Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Purpose: New insight into the extent of the target volume for the postoperative irradiation of malignant pleural mesothelioma as determined during surgery has indicated that standard conformal radiotherapy (IMRT) is not sufficient for curative treatment. We describe a novel technique for implementing intensity-modulated radiotherapy (IMRT) to deliver higher doses to treat the full extent of these complex target volumes.

Methods And Materials: After extrapleural pneumonectomy, 7 patients underwent simulation, treatment planning, and treatment with IMRT to the involved hemithorax and adjacent abdomen. The target volumes encompassed the entire operative bed, including the ipsilateral mediastinum, anterior pleural reflection, and ipsilateral pericardium and the insertion of the diaphragm and crura. These were extensively marked during surgery with radiopaque markers to facilitate target delineation.

Results: Setup uncertainty and respiratory-dependent motion were found to be small. Coverage of the planning target volume was very good, with the crus of the diaphragm the most difficult volume to irradiate. The radiation doses to normal structures were acceptable.

Conclusion: IMRT for treatment of malignant mesothelioma after extrapleural pneumonectomy results in more potentially curative doses to large, complex target volumes with acceptable doses to normal tissues.
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http://dx.doi.org/10.1016/s0360-3016(02)04150-0DOI Listing
March 2003

Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody.

Anticancer Drugs 2003 Jan;14(1):49-56

Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.

Epidermal growth factor receptor (EGFR) plays an important role in cell division and cancer progression, as well as angiogenesis and metastasis. Since many tumor cells exhibit the EGFR on their surface, functional imaging of EGFR provides not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-EGFR therapy could be assessed effectively. C225 is a chimeric monoclonal antibody that targets the human extracellular EGFR and inhibits the growth of EGFR-expressing tumor cells. Also, it has been demonstrated that C225, in combination with chemotherapeutic drugs or radiotherapy, is effective in eradicating well-established tumors in nude mice. We have developed 99mTc-labeled C225 using ethylenedicysteine (EC) as a chelator. This study aimed at measuring uptake of 99mTc-EC-C225 in EGFR+ tumor-bearing animal models and preliminary feasibility of imaging patients with head and neck carcinomas. In vitro Western blot analysis and cytotoxicity assays were used to examine the integrity of EC-C225. Tissue distribution studies of 99mTc-EC-C225 were evaluated in tumor-bearing rodents at 0.5-4 h. In vivo biodistribution of 99mTc-EC-C225 in tumor-bearing rodents showed increased tumor-to-tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-C225 to assess EGFR expression. SPECT images confirmed that the tumors could be visualized with 99mTc-EC-C225 from 0.5 to 4 h in tumor bearing rodents. We conclude that 99mTc-EC-C225 may be useful to assess tumor EGFR expression. This may be useful in the future for selecting patients for treatment with C225.
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http://dx.doi.org/10.1097/00001813-200301000-00007DOI Listing
January 2003