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• W2059443275 abstract "Recent developments in image-guided radiotherapy are ushering in a new era of radiotherapy for lung cancer. Positron emission tomography/computed tomography (PET/CT) has been shown to improve targeting accuracy in 25 to 50% of cases, and four-dimensional CT scanning helps to individualize radiotherapy by accounting for tumor motion. Daily on-board imaging reduces treatment set-up uncertainty and provides information about daily organ motion and variations in anatomy. Image-guided intensity-modulated radiotherapy may allow for the escalation of radiotherapy dose with no increase in toxicity. More importantly, treatment adaptations based on anatomic changes during the course of radiotherapy and dose painting within involved lesions using functional imaging such as PET may further improve clinical outcomes of lung cancer patients and potentially lead to new clinical trials. Image-guided stereotactic radiotherapy can achieve local control rates exceeding 90% through the use of focused, hypofractionated, highly biologically effective doses. These novel approaches were considered experimental just a few years ago, but accumulating evidence of their potential for significantly improving clinical outcomes is leading to their inclusion in standard treatments for lung cancer at major cancer centers. In this review article, we focus on novel image-guided radiotherapy approaches, particularly PET/CT and four-dimensional CT-based radiotherapy planning and on-board image-guided delivery, stereotactic radiotherapy, and intensity-modulated radiotherapy for mobile nonsmall cell lung cancer. Recent developments in image-guided radiotherapy are ushering in a new era of radiotherapy for lung cancer. Positron emission tomography/computed tomography (PET/CT) has been shown to improve targeting accuracy in 25 to 50% of cases, and four-dimensional CT scanning helps to individualize radiotherapy by accounting for tumor motion. Daily on-board imaging reduces treatment set-up uncertainty and provides information about daily organ motion and variations in anatomy. Image-guided intensity-modulated radiotherapy may allow for the escalation of radiotherapy dose with no increase in toxicity. More importantly, treatment adaptations based on anatomic changes during the course of radiotherapy and dose painting within involved lesions using functional imaging such as PET may further improve clinical outcomes of lung cancer patients and potentially lead to new clinical trials. Image-guided stereotactic radiotherapy can achieve local control rates exceeding 90% through the use of focused, hypofractionated, highly biologically effective doses. These novel approaches were considered experimental just a few years ago, but accumulating evidence of their potential for significantly improving clinical outcomes is leading to their inclusion in standard treatments for lung cancer at major cancer centers. In this review article, we focus on novel image-guided radiotherapy approaches, particularly PET/CT and four-dimensional CT-based radiotherapy planning and on-board image-guided delivery, stereotactic radiotherapy, and intensity-modulated radiotherapy for mobile nonsmall cell lung cancer. Radiation therapy plays a crucial role in the management of lung cancer. However, with two-dimensional (2-D) radiotherapy planning, the local control was poor and dose escalation was associated with increased toxicity, particularly when concurrent chemotherapy was given.1Curran W Scott C Langer C et al.Long term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresectable NSCLC:RTOG 9410.Proc Am Soc Clin Oncol. 2003; 22: 621aGoogle Scholar Three-dimensional (3-D) conformal radiotherapy (3-D CRT) might improve local control and possibly survival compared with 2-D therapy in stage I nonsmall cell lung cancer (NSCLC).2Fang L Komaki R Allen P Guerrero T Mohan R Cox J Comparison of outcomes for patients with medically inoperable Stage I non-small-cell lung cancer treated with two-dimensional vs. three-dimensional radiotherapy.Int J Radiat Oncol Biol Phys. 2006; 66: 108-116Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar In addition, dose-escalation phase I/II clinical studies have shown promising clinical outcomes in stage III NSCLC, with improvements in survival and toxicity, with the use of 3-D CRT, although a phase III study is needed to confirm the results.3Socinski M Rosenman J Halle J et al.Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B non-small-cell lung carcinoma.Cancer. 2001; 92: 1213-1223Crossref PubMed Scopus (145) Google Scholar, 4Schild S McGinnis W Graham D et al.Results of a phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2006; 65: 1106-1111Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar The three main reasons for local failure after radiotherapy are (1) geographic misses due to inadequacy of imaging tools for staging and radiotherapy planning; (2) geographic misses due to respiratory tumor motion during radiation delivery; and (3) inadequate radiation dose because of the potential for significant toxicity. Image-guided radiotherapy (IGRT), particularly radiotherapy planning based on positron emission tomography/computed tomography (PET/CT), consideration of individualized tumor motion with four-dimensional (4-D) CT, and on-board imaging-guided adapted radiotherapy during the course of treatment may allow more accurate tumor targeting and reduce side effects. IGRT with radiation dose escalation or acceleration could significantly improve clinical outcomes for patients with lung cancer. For example, image-guided stereotactic body radiotherapy (SBRT) has been shown in phase II clinical trials to improve local control and survival in early-stage NSCLC compared with historical data,5Xia T Li H Sun Q et al.Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2006; 66: 117-125Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar, 6Onishi H Araki T Shirato H et al.Stereotactic hypofractionated high-dose irradiation for stage I non-small cell lung carcinoma clinical outcome in 245 subjects in a Japanese multi-institutional study.Cancer. 2004; 101: 1623-1631Crossref PubMed Scopus (709) Google Scholar, 7Nagata Y Takayama K Matsuo Y et al.Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame.Int J Radiat Oncol Biol Phys. 2005; 63: 1427-1431Abstract Full Text Full Text PDF PubMed Scopus (541) Google Scholar, 8Chang JY Balter P Dong L et al.4-D CT based and daily in-room CT-guided stereotactic body radiotherapy (SBRT) in lung cancer.Int J Radiat Oncol Biol Phys. 2007; 69: S88Abstract Full Text Full Text PDF PubMed Google Scholar, 9Chang JY Roth JA Stereotactic body radiation therapy for stage I NSCLC.Thorac Surg Clin. 2007; 17: 251-259Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar and intensity-modulated radiotherapy (IMRT) may be better tolerated10Yom S Liao Z Liu H et al.Analysis of acute toxicity results of intensity modulated radiation therapy (IMRT) in the treatment of non-small cell lung cancer (NSCLC) (O-152a).Lung Cancer. 2005; 49: S52Abstract Full Text PDF Google Scholar, 11Chang JY Liu H Komaki R Intensity modulated radiation therapy and proton radiotherapy for non-small-cell lung cancer.Curr Oncol Rep. 2005; 7: 255-259Crossref PubMed Scopus (26) Google Scholar than 3-D CRT. As information about IGRT for lung cancer continues to emerge, “standard” radiotherapy approaches for patients with NSCLC are evolving. Guidelines and step-by-step techniques for the use of IGRT in mobile lung cancers are needed to implement IGRT into daily clinical practice. In this review, we discuss the role of radiotherapy in NSCLC and our recommendations/suggestions and techniques for IGRT design and adapted radiotherapy to take intrafraction and interfraction tumor motion into consideration. Guidelines from the International Commission on Radiation Units Report No. 5012International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon beam therapy. Bethesda, MD; 1993. Report No.: 50.Google Scholar for defining targets have been applied to the treatment of lung cancer. The gross tumor volume (GTV) is defined as tumor that is visible by any imaging modality (the primary tumor) along with any grossly involved lymph nodes. The clinical target volume (CTV) is the anatomically defined area (e.g., the hilar or mediastinal lymph nodes or a margin around the grossly visible disease) believed to harbor microscopic disease. The planning target volume (PTV) includes a margin around the CTV to account for physiologic organ motion during treatment and day-to-day set-up errors in fractionated therapy. The target volumes are defined by image-guided procedures as follows. The pulmonary extent of lung tumors should be delineated on pulmonary windows and level settings in CT images, and the mediastinal extent of tumors should be delineated using mediastinal windows and level settings. In general, a lymph node larger than 1 cm in its shortest dimension on CT is considered positive, because the risk of involvement is more than 15%.13Onn A, Vaprociyan AA, Chang JY, et al. Cancer of the lung. Cancer Med Editors: Holland-Frei, version 7; 2007:1179–1225.Google Scholar Functional imaging such as fluorodeoxyglucose (FDG)-PET is quite important for disease staging14Pieterman R van Putten J Meuzelaar J et al.Preoperative staging of non-small-cell lung cancer with positron-emission tomography.N Engl J Med. 2000; 343: 254-261Crossref PubMed Scopus (1011) Google Scholar and radiation treatment volume delineation15Bradley J Thorstad W Mutic S et al.Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2004; 59: 78-86Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, 16Mac Manus MP D'Costa I Evritt S et al.Comparison of CT and PET/CT coregistered images in planning radical radiotherapy in patients with non-small cell lung cancer.Australas Radiol. 2007; 51: 386-393Crossref PubMed Scopus (18) Google Scholar in NSCLC, particularly in stage III disease. In particular, FDG-PET can help to categorize suspected mediastinal and hilar lymph node adenopathy and distinguish benign collapsed lung tissue from tumor (Figure 1A, B). There are still many unresolved questions and controversies in FDG-PET-guided radiotherapy planning.17Nestle U Kremp S Grosu A Practical integration of F18-FDG-PET and PET-CT in the planning of radiotherapy for non-small cell lung cancer: The technical basis, ICRU-target volumes, problems, prospectives.Radiother Oncol. 2006; 81: 209-225Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar Several approaches have been suggested for defining malignant GTV using FDG-PET: (1) visual interpretation of the FDG-PET image and tumor contours18Kiffer JD Berlangierri SU Scott AM et al.The contribution of 18F-fluoro-2-deoxy-glucose PET imaging to radiotherapy planning in lung cancer.Lung Cancer. 1998; 19: 167-177Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar; (2) using a percentage (e.g., 40 or 50%) of the maximal uptake as the threshold for radiotherapy target volume delineation15Bradley J Thorstad W Mutic S et al.Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2004; 59: 78-86Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar; and (3) using a threshold for image segmentation, although the optimal value has not been well defined. Currently, a standard uptake value (SUV) equal to or higher than 2.5 is suggested as a threshold.19Hong R Halama J Bova D Sethi A Emami B Correlation of PET standard uptake value and CT window-level thresholds for target delineation in CT-based radiation treatment planning.Int J Radiat Oncol Biol Phys. 2007; 67: 720-726Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar However, the SUV is determined not only by the presence of cancer but also by the size of the lesion, presence of inflammation, timing of imaging after injection of 18F-FDG, blood glucose level, etc. FDG-PET scanning usually can only detect cancer lesions larger than 5 to 10 mm. For smaller lesions, clinical judgment should be applied. Inflammation can cause false-positive findings on FDG-PET scans, and biopsy is recommended in the event of questionable findings (Figure 1C). Pre- and posttreatment SUVs of FDG-PET were found to be predictive of survival in NSCLC.20Sasaki R Komaki R Macapinlac H et al.Fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.J Clin Oncol. 2005; 23: 1136-1143Crossref PubMed Scopus (255) Google Scholar, 21Mac Manus MP Hicks RJ Matthews JP et al.Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small cell lung cancer.J Clin Oncol. 2003; 21: 1285-1292Crossref PubMed Scopus (382) Google Scholar Recent clinical data have also shown that in NSCLC treated with standard concurrent chemoradiotherapy, an SUV higher than 13.8 was associated with a local recurrence rate of 65.5% compared with a rate of <25% in lesions with an SUV <13.8.22Klopp A Chang JY Liu H et al.Intra-thoracic patterns of failure for non-small-cell lung cancer (NSCLC) with PET/CT-defined target delineation (2463a).Int J Radiat Oncol Biol Phys. 2006; 66: S467Abstract Full Text Full Text PDF Google Scholar In theory, with specific radioactive tracers, functional imaging techniques such as PET can visualize biologic pathways with particular significance for tumor response to therapy, such as higher SUVs, hypoxia, and altered gene expression. These subvolumes of the tumor can serve as a “target in a target” and allow for dose painting using IMRT.23Bentzen SM Radiation therapy: intensity modulated, image-guided, biologically optimized and evidence based.Radiother Oncol. 2004; 77: 227-230Abstract Full Text Full Text PDF Scopus (48) Google Scholar, 24Tanderup K Olsen D Grau C Dose painting: art or science?.Radiother Oncol. 2006; 79: 245-248Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Because PET scans are acquired over multiple breathing cycles, as opposed to the “snapshots” acquired with CT imaging, significant image mismatch can occur using conventional PET/CT if the tumor moves more than 5 mm during the breathing cycle. 4-D CT-based attenuation correction of PET or gated PET is recommended if the tumor moves significantly.25Pan T Luo D Liu H et al.Improving tumor localization and standard uptake value quantitation of non-small cell lung cancer and esophageal cancer patients by new respiration-averaged CT in PET/CT imaging (2466a).Int J Radiat Oncol Biol Phys. 2006; 66: S468-S469Abstract Full Text Full Text PDF Google Scholar A radiographic–histopathologic study of lung parenchymal disease26Giraud P Antoine M Larrouy A et al.Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.Int J Radiat Oncol Biol Phys. 2000; 48: 1015-1024Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar demonstrated that GTV-to-CTV expansions of 6 mm for squamous cancers and 8 mm for adenocarcinomas are required to cover the gross tumor and microscopic disease with 95% accuracy. Expansions for other histologic tumor types have not been determined, but a conservative approach would be to use 8 mm. An appropriate CTV for mediastinal involvement has not been rigorously determined. An abstract presented at the 2006 meeting of the American Society for Therapeutic Radiology and Oncology indicated that the maximal microscopic extension of involved lymph nodes is between 0.5 and 8.9 mm (average, 3.2 mm).27Yu J Meng X Xing L et al.The study on correlation between F-18 FDG PET/CT standard uptake value and clinical target volume definition in radiotherapy for non-small-cell lung cancer (2484a).Int J Radiat Oncol Biol Phys. 2006; 66: S480Abstract Full Text Full Text PDF Google Scholar Based on this information, we use 8-mm expansions around involved nodes (those showing gross involvement or positive findings on FDG-PET). Obviously, these expansions should not necessarily be applied uniformly along all axes and should always be individualized on the basis of the location of the primary tumor and involved lymph node. In the absence of radiographic proof of invasion, the CTV of the primary lesion should not extend into the chest wall or mediastinum. CTV expansions for lymph node disease should not extend into the major airways or the lung, chest wall, or vertebral body without evidence of invasion on CT or magnetic resonance imaging. Restricting the target volume to gross disease or omitting elective nodal irradiation for the treatment of NSCLC remains the subject of debate. Previous studies using CT-based planning reported low rates of isolated out-of-field recurrences, in the range of 0 to 6.4%, suggesting that this approach is reasonable.28Sulman E Chang JY Liao Z et al.Exclusion of elective nodal irradiation does not decrease local regional control of non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2005; 63: S226-S227Abstract Full Text Full Text PDF Google Scholar, 29Senan S Burgers J Samson M et al.Can elective nodal irradiation be omitted in Stage III non-small-cell lung cancer? An analysis of recurrences after sequential chemotherapy and “involved-field” radiotherapy to 70 Gy.Int J Radiat Oncol Biol Phys. 2001; 51: 21Abstract Full Text Full Text PDF Google Scholar, 30Martel M Sahijdak W Hayman J Ball D Incidental dose to clinically negative nodes from conformal treatment fields for non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 1997; 45: 244Abstract Full Text PDF Google Scholar, 31Bradley J Graham MV Winter K et al.Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.Int J Radiat Oncol Biol Phys. 2005; 61: 318-328Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar A multicenter study (RTOG 9311) also showed that the elective nodal irradiation failure rate was <8%.31Bradley J Graham MV Winter K et al.Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.Int J Radiat Oncol Biol Phys. 2005; 61: 318-328Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar A recent study22Klopp A Chang JY Liu H et al.Intra-thoracic patterns of failure for non-small-cell lung cancer (NSCLC) with PET/CT-defined target delineation (2463a).Int J Radiat Oncol Biol Phys. 2006; 66: S467Abstract Full Text Full Text PDF Google Scholar showed that limiting the target volume to PET-positive disease was associated with a similar low rate of isolated out-of-field failure (5.7%). However, the low rate of isolated out-of-field failures is in part a consequence of high rates of in-field failures. As the risk of in-field failures decreases with increasing dose or the use of new radiosensitizers, the rates of elective nodal failures may increase. Currently, it seems reasonable to omit elective nodal irradiation to limit toxicity, but this may need to be reevaluated when local control improves. The PTV is defined as the CTV plus a margin to account for daily set-up error and target motion (Figure 2). Our unpublished data show that when patients are immobilized with a Vac-Loc bag and T-bar, an expansion of 7 mm along all axes accounts for 95% of the day-to-day uncertainty in set-up. Set-up uncertainty probably is a function of both the technique and the institutional practices and should be measured for each individual undergoing each type of technique. In our institution, use of a daily kV image can reduce the set-up uncertainty to 5 mm. Use of a daily on-board image such as with CT on-rails or cone-beam CT before each radiotherapy fraction can reduce the day-to-day setup uncertainty to 3 mm (unpublished data). Consideration of tumor motion is critical for lung cancer radiotherapy and, thus, is discussed at some length in the following paragraphs. A major obstacle to radiotherapy target delineation has been respiration-induced target motion (also known as intrafractional tumor motion), which can add considerable geometrical uncertainty to the radiation treatment. Such motion requires enlargement of the treatment field portals to cover the movement of the tumor during treatment. The development of 4-D CT with multislice detectors and faster imaging reconstruction has facilitated the ability to obtain images while patients breathe and to assess organ motion.32Nehmeh S Erdi Y Pan T et al.Four-dimensional (4D) PET/CT imaging of the thorax.Med Phys. 2004; 31: 3179-3186Crossref PubMed Scopus (276) Google Scholar 4-D CT involves acquiring over-sampled CT information and correlating these data with information about the respiratory cycle (Figure 2A). Tumor motion is best assessed individually for each patient. For patients in whom the tumor moves <5 mm, simply expanding the PTV margin is adequate. However, for patients with substantial tumor motion, particularly more than 1 cm, an individualized tumor motion margin should be considered. A 4-D CT study33Liu H Balter P Tutt T et al.Assessing respiration-induced tumor motion and internal target volume using 4DCT for radiation therapy of lung cancer.Int J Radiat Oncol Biol Phys. 2007; 68: 531-540Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar showed that more than 50% of tumors moved more than 5 mm during treatment, and 10.8% moved more than 1 cm (possibly as much as 3–4 cm), particularly lesions close to the diaphragm. To address tumor motion, the International Commission on Radiation Units Report 62 in 1999 introduced the concept of internal target volume (ITV), which combines the ventilatory or other intrafractional target motion margin and the CTV (Figure 2B). A 4-D CT simulation is desirable for evaluating tumor motion and for providing an individualized assessment of the target volume and margin. Patients should be evaluated for regularity of breathing, responsiveness to feedback guidance, breath-holding capability, and suitability for implantation of fiducial markers. The findings of this evaluation should then be used to select one of the following treatment-delivery techniques: free breath, breath-hold, ventilatory gating, or motion tracking. When 4-D CT is available for treatment planning, we propose the use of a new concept called internal gross tumor volume (IGTV; Figure 2C), which is the envelope of the GTV throughout its motion during respiration. Delineating the IGTV from 4-D CT images involves outlining the tumor volume on the expiratory phase of the 4-D images and registering the outline on other phases of the images to create a union of target contours enclosing all possible positions of the target. Another method is to create an image of maximum intensity projection by combining data from the multiple CT data sets with data from the whole-breath cycle and modify tumor volume by visual verification of the target volume throughout 10 breathing phases (10 phases were chosen based on the practical signal-to-noise ratio, reconstruction time, and radiation dose exposure, see Ref. 34Ezhil M Vedam S Choi B Starkschall P Balter J Chang JY Determination of patient-specific intra-fractional respiratory motion envelope of tumors from maximum intensity projections of 4D datasets.Int J Radiat Oncol Biol Phys. 2007; 68: S484Abstract Full Text Full Text PDF Google Scholar). In this case, the ITV should consist of the IGTV plus a margin to account for microscopic disease (8 mm). Even with 4-D CT, the free-breathing simulation is only a snapshot and a single stochastic sampling of the patient's breathing. Attention should be paid to irregular breathing and variations in the patient's breathing pattern over the course of each treatment session and the entire treatment course and to the effects of these irregularities on the ITV margin (see late discussion; Refs. 35Vedam S Dong L Zhang J et al.Impact of respiration-induced tumor motion uncertainties on adaptive treatment delivery strategies: a comparison through repeat 4D CT imaging.Int J Radiat Oncol Biol Phys. 2006; 66: 614Abstract Full Text Full Text PDF Google Scholar, 36Britton K Starkschall G Pan T Chang JY Mohan R Komaki R Assessment of gross tumor volume regression and motion changes during radiotherapy for non-small-cell lung cancer as measured by four-dimensional computed tomography (4-DCT).Int J Radiat Oncol Biol Phys. 2007; 68: 1036-1046Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). If 4-D CT is not available, alternative approaches such as those that follow should be used to account for tumor motion. If a patient is unable to hold his breath during the delivery of radiation, an ITV can be developed based on breath-hold spiral CT images that require the patient to hold his breath once during the simulation at the end of expiration and once at the end of inspiration but not during treatment delivery. In this procedure, images are acquired through the use of a standard extended temporal thoracic CT protocol. In this protocol, patients are asked to breathe normally, and the extended temporal CT images are acquired at the beginning of the simulation; the isocenter is then set. Subsequently, images are obtained by using a fast CT simulation protocol while at 100% tidal volume (end of inspiration) and 0% tidal volume (end of expiration). The traces from the real-time position management system should be recorded. Separate GTVs and CTVs should be delineated by a physician both at the end of expiration CT image set and at the end of inspiration image set (Figure 2C). An ITV is then generated by combining the two CTVs on the extended temporal CT scan to form an ITV that includes the entire path of the CTV as it moves from inspiration to expiration. A 3-mm margin should be added to account for uncertainties of tumor motion and image registration. Normal tissues should be contoured in the extended temporal CT images as well. The IVT should be superimposed on the slow CT images, which will serve as the basis for treatment planning. The breath-hold treatment-delivery method is the most accurate for patients who are able to comply. Two techniques are in common use for breath-holding at reproducible points in the respiratory cycle—active breathing control and deep inspiration breath-hold.37Rosenzweig KE Hanley J Mah D et al.The deep inspiration breath-hold technique in the treatment of inoperable non-small-cell lung cancer.Int J Radiat Oncol Biol Phys. 2000; 48: 81-87Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar, 38Gagel B Demirel C Kientopf A et al.Active breathing control (ABC): determination and reduction of breathing-induced organ motion in the chest.Int J Radiat Oncol Biol Phys. 2007; 67: 742-749Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar The radiation beam is initiated while the breath is being held. With these techniques, respiratory tumor excursion is limited to fixed volumes and diaphragm excursion is limited to about 5 mm instead of 10 to 15 mm. These techniques require cooperative patients who are able to hold their breaths for at least 15 seconds. Unfortunately, patients with poor pulmonary function (those who would most benefit from minimizing the irradiated lung volume) are the least able to comply with breath-hold techniques. Their breathing also tends to be irregular during the delivery of radiation. When available, the ventilatory gating method39Ramsey C Scaperoth D Arwood D Oliver A Clinical efficacy of respiratory gated conformal radiation therapy.Med Dosim. 1999; 24: 115-119Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar can be used to treat patients who cannot hold their breaths for the breath-hold treatment delivery but can breathe regularly and reproducibly. Several commercially available systems can be used with this technique, in which an externally placed fiducial marker is tracked as the patient breathes. The beam can be triggered at a chosen point in the ventilatory cycle, typically at end-expiration because it is the longest and most reproducible portion of the ventilatory cycle. Ventilatory-gated therapy seems to spare more normal structures such as the lung for patients with tumor volumes <100 cm3 (usually <5 cm in diameter if the tumor is almost round) and tumor motion of more than 1 cm. In general, tumors in the lower lobes of the lung move more than those in other locations during breathing. An optimal margin with gated treatment is dependent on patient breath regularity and the technique used. A 5-mm margin is suggested to allow for the uncertainty of day-to-day tumor localization from gating.40Starkschall G, Nelson C, Morice R, Stevens C, Chang JY. Use of portal imaging and implanted fiducial to assess respiratory motion in gated radiotherapy, 9th international workshop on electronic portal imaging, 2006:146–147.Google Scholar The motion tracking approach is described in the on-board image and real-time tracking sections. Two-dimensional (2-D) radiographic imaging such as with the megavoltage (MV) electronic portal imaging device (EPID) is t" @default.
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• W2059443275 title "Image–Guided Radiation Therapy for Non–small Cell Lung Cancer" @default.
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