Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy.

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience.

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. RESULTS: This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3-4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3-4 fractions. CONCLUSIONS: This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

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

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/ß= 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.

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.

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 vs. 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.

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.

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 v 12.1% and 17.4% in the HD arm, respectively (P = .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 v 20.3 months (P = .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% (P = .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.

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

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.

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

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).

Promise and pitfalls of quantitative imaging in oncology clinical trials.

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.

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

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.

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

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.

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

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.

Functional lung imaging in thoracic cancer radiotherapy.

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.

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

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.

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

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.

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

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.

Radiotherapy for mesothelioma.

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.

Extracranial stereotactic radiation delivery.

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.

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

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.

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

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.