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Background and Purpose: To study the effect of breathing motion on gross tumor volume (GTV) coverage for lung tumors using dose-volume histograms and relevant dosimetric indices., Patients and Methods: Treatment plans were chosen for 12 patients treated at our institution for lung carcinoma. GTV volumes of these patients ranged from 1.2 to 97.3 cm(3). A margin of 1-2 cm was used to generate the planning target volume (PTV). Additional margins of 0.6-1.0 cm were added to the PTV when designing treatment portals. For the purposes of TCP calculation, the prescription dose was assumed to be 70 Gy to remove the effects of prescription differences. Setup error was incorporated into the evaluation of treatment plans with a systematic component of sigma(RL) = 0.2 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.3 cm and a random component of sigma(RL) = 0.3 cm, sigma(AP) = 0.3 cm, and sigma(SI) = 0.3 cm. Breathing motion was incorporated into these plans based on an independent analysis of fluoroscopic movies of the diaphragm for 7 patients. The systematic component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated into the treatment plans on a slice by slice basis. The intrafractional component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated by averaging the dose calculation over all displacements of the breathing cycle. Each patient was simulated 500 times to discern the range of possible outcomes. The simulations were repeated for a worst case scenario which used only breathing data with a large diaphragmatic excursion, both with and without intrafractional breathing motion., Results: Dose to 95% of the GTV (D95), volume of the GTV receiving 95% of the prescription dose (V95) and TCP changed an average of -1.4+/-4.2, -1.0+/-3.3, and -1.4+/-3.8%, respectively, with the incorporation of normal breathing effects. In the worst case scenario (heavy breathers), D95 and V95 changed an average of -9.8+/-10.1 and -8.3+/-11.3%, respectively, and TCP changed by -8.1+/-9.1%. GTVs with volumes greater than 60 cm(3) showed stronger sensitivity to breathing especially if the shape was non-ellipsoidal. In the normal breathing case, the probability of a decrease in D95, V95, or TCP of a magnitude greater than 10% is less than 4%, and in the worse case scenario this probability is approximately 30-40% with intrafractional breathing motion included, and less than 10% with intrafractional breathing motion not included., Conclusions: With the PTV margins routinely used at our center, the effects of normal breathing on coverage are small on the average, with a less than 4% chance of a 10% or greater decrease in D95, V95, or TCP. However, in patients with large respiration-induced motion, the effect can be significant and efforts to identify such patients are important.

We examine 2 strategies for reducing respiration-induced organ motion in radiation treatment: deep inspiration breath hold (DIBH) and respiratory gating. DIBH is a controlled breathing technique in which the patient performs a supervised breath hold during treatment. The technique offers 2 benefits: reduced respiratory motion from the breath hold and increased normal tissue sparing from the increased lung volume. In respiratory-gated treatment, a device external to the patient monitors breathing and allows delivery of radiation only during certain time intervals, synchronous with the patient's respiratory cycle. Gated treatment offers reduced respiratory motion with less patient effort than DIBH. We briefly survey the development of these 2 strategies, describe their clinical implementation for treatment of thoracic and liver tumors at the Memorial Sloan-Kettering Cancer Center, and discuss their advantages and limitations.

Intensity-modulated radiation therapy can be conveniently delivered with a multileaf collimator. With this method, the entire field is not delivered at once, but rather it is composed of many subfields defined by the leaf positions as a function of beam on time. At any given instant, only these subfields are delivered. During treatment, if the organ moves, part of the volume may move in or out of these subfields. Due to this interplay between organ motion and leaf motion the delivered dose may be different from what was planned. In this work, we present a method that calculates the effects of organ motion on delivered dose. The direction of organ motion may be parallel or perpendicular to the leaf motion, and the effect can be calculated for a single fraction or for multiple fractions. Three breast patients and four lung patients were included in this study,with the amplitude of the organ motion varying from +/- 3.5 mm to +/- 10 mm, and the period varying from 4 to 8 seconds. Calculations were made for these patients with and without organ motion, and results were examined in terms of isodose distribution and dose volume histograms. Each calculation was repeated ten times in order to estimate the statistical uncertainties. For selected patients, calculations were also made with conventional treatment technique. The effects of organ motion on conventional techniques were compared relative to that on IMRT techniques. For breast treatment, the effect of organ motion primarily broadened the penumbra at the posterior field edge. The dose in the rest of the treatment volume was not significantly affected. For lung treatment, the effect also broadened the penumbra and degraded the coverage of the planning target volume (PTV). However, the coverage of the clinical target volume (CTV) was not much affected, provided the PTV margin was adequate. The same effects were observed for both IMRT and conventional treatment techniques. For the IMRT technique, the standard deviations of ten samples of a 30-fraction calculation were very small for all patients, implying that over a typical treatment course of 30 fractions, the delivered dose was very close to the expected value. Hence, under typical clinical conditions, the effect of organ motion on delivered dose can be calculated without considering the interplay between the organ motion and the leaf motion. It can be calculated as the weighted average of the dose distribution without organ motion with the distribution of organ motion. Since the effects of organ motion on dose were comparable for both IMRT and conventional techniques, the PTV margin should remain the same for both techniques.

Purpose: Megavoltage cone-beam computed tomography (MVCBCT) has been proposed for treatment verification in conformal radiotherapy. However, the doses required for such imaging may compromise the quality of the delivered dose distribution. The present paper explores the effect of cone-beam imaging on dose homogeneity and critical organ dose and the use of our new tool, adapted intensity-modulated radiation therapy (AIMRT)., Methods and Materials: Three types of treatment plans were devised (3D-CRT [three-dimensional conformal radiotherapy], IMRT [intensity-modulated radiotherapy], and AIMRT) based on 4 patients with thoracic malignancies. MVCBCT fields were then integrated into the plans. The MVCBCT technique used 21 imaging portals at 10 degrees intervals. The MVCBCT apertures were shaped to conform to the planning target volume with a 6-mm margin. In a second set of plans, the field size was expanded by a further 2 cm. The unoptimized MVCBCT dose distribution was incorporated into the IMRT plan using AIMRT., Results: Normal-tissue complication probability with MVCBCT is acceptable for all plans at the 66.6 Gy level, but exceeds tolerance for both 3D-CRT alone and 3D-CRT with MVCBCT at higher doses. In contrast, the use of AIMRT planning with MVCBCT allowed safe dose escalation to 85 Gy. Expanding the MVCBCT aperture provided better anatomic visibility with an acceptable lung dose. The results using IMRT with MVCBCT fell between the values measured for 3D-CRT and AIMRT with MVCBCT., Conclusion: The present study is the first to demonstrate that MVCBCT can be incorporated into 3D-CRT and IMRT planning with minimal effect on planning target volume homogeneity and dose to critical structures. This paves the way for highly conformal radiotherapy at greater doses delivered with increased confidence and safety.

Purpose: To determine the clinical impact of the Varian Real-Time Position Monitor (RPM) respiratory gating system for treatment of liver tumors., Methods and Materials: Ten patients with liver tumors were selected for evaluation of this passive system, which tracks motion of reflective markers mounted on the abdomen with an infrared-sensitive camera. At simulation, a fluoroscopic movie, breathing trace, and CT scans synchronized at end-expiration (E-E) and end-inspiration were acquired in treatment position using the RPM system. Organs and gross tumor volume were contoured on each CT. Each organ's positional change between two scan sets was quantified by calculation of the center of volume shift and an "index coefficient," defined as the volume common to the two versions of the organ to the volume included in at least one (intersection/union). Treatment dose was determined by use of normal tissue complication probability calculations and dose-volume histograms. Gated portal images were obtained to monitor gating reproducibility with treatment., Results: Eight patients received 177 treatments with RPM gating. Average superior-to-inferior (SI) diaphragm motion on initial fluoroscopy was reduced from 22.7 mm without gating to 5.1 mm with gating. Comparing end-inspiration to E-E CT scans, average SI movement of the right diaphragm was 11.5 mm vs. 2.2 mm for two E-E CT scans. For all organs, average E-I SI organ motion was 12.8 mm vs. 2.0 mm for E-E studies. Index coefficients were closer to 1.0 for E-E than end-inspiration scans, indicating gating reproducibility. The average SI displacement of diaphragm apex on gated portal images compared with DRR was 2.3 mm. Treatment was prolonged less than 10 minutes with gating. The reproducible decrease in organ motion with gating enabled reduction in gross tumor volume-to-planning target volume margin from 2 to 1 cm. This allowed for calculated dose increases of 7%-27% (median: 21.3%) in 6 patients and enabled treatment in 2., Conclusion: Gating of radiotherapy for liver tumors enables safe margin reduction on tumor volume, which, in turn, may allow for dose escalation.

Many lung cancer patients who undergo radiation therapy are treated with higher energy photons (15-18 MV) to obtain deeper penetration and better dose uniformity. However, the longer range of the higher energy recoil electrons in the low-density medium may cause lateral electronic disequilibrium and degrade the target coverage. To compare the dose homogeneity achieved with lower versus higher energy photon beams, we performed a dosimetric study of 6 and 15 MV three-dimensional (3D) conformal treatment plans for lung cancer using an accurate, patient-specific dose-calculation method based on a Monte Carlo technique. A 6 and 15 MV 3D conformal treatment plan was generated for each of two patients with target volumes exceeding 200 cm(3) on an in-house treatment planning system in routine clinical use. Each plan employed four conformally shaped photon beams. Each dose distribution was recalculated with the Monte Carlo method, utilizing the same beam geometry and patient-specific computed tomography (CT) images. Treatment plans using the two energies were compared in terms of their isodose distributions and dose-volume histograms (DVHs). The 15 MV dose distributions and DVHs generated by the clinical treatment planning calculations were as good as, or slightly better than, those generated for 6 MV beams. However, the Monte Carlo dose calculation predicted increased penumbra width with increased photon energy resulting in decreased lateral dose homogeneity for the 15 MV plans. Monte Carlo calculations showed that all target coverage indicators were significantly worse for 15 MV than for 6 MV; particularly the portion of the planning target volume (PTV) receiving at least 95% of the prescription dose (V(95)) dropped dramatically for the 15 MV plan in comparison to the 6 MV. Spinal cord and lung doses were clinically equivalent for the two energies. In treatment planning of tumors that abut lung tissue, lower energy (6 MV) photon beams should be preferred over higher energies (15-18 MV) because of the significant loss of lateral dose equilibrium for high-energy beams in the low-density medium. Any gains in radial dose uniformity across steep density gradients for higher energy beams must be weighed carefully against the lateral beam degradation due to penumbra widening.

Intensity modulated radiotherapy (IMRT) beams may have strong fluence variations and are advantageous at disease sites such as lung and head and neck (H&N), where neighboring tissues have very different electron densities. We use Monte Carlo (MC) dose calculations to evaluate the dosimetric effects of these inhomogeneities for 10 clinical IMRT treatment plans for five lung patients and four H&N patients. All beams are 6 MV photons. "Standard plans" were first produced on a clinical treatment planning system which optimizes beam intensity distributions to meet dose and dose-volume constraints and calculates dose using a measurement-based pencil-beam algorithm with an equivalent pathlength inhomogeneity correction. Patient anatomy and electron densities were obtained from patient-specific CT images. The dose distribution of each beam was recalculated with the MC method, using the same CT images, beam geometry, beam weighting and optimized fluence intensity distributions as the corresponding standard plan. For the lung cases, the MC calculated dose distributions are characterized by reduced penetrations and increased penumbra due to larger secondary electron range in the low-density media, which is not accurately accounted for in the pencil beam algorithm. For the lung cases, the PTV was underdosed; except for one dose-volume index, underdose was less than 10%. Individual H&N fields are affected to different degrees by tissue inhomogeneities, depending on specific anatomy, especially the size and location of air cavities in relation to the beam orientation and field size. For four H&N plans, PTV coverage changed by less than 2%; for the fifth, there was less than 10% difference between the standard and the MC plans. Critical normal tissue DVHs (cord, lung, brainstem) are changed by <10% at the high dose end and mean lung doses are changed by <6%.

Purpose: To analyze acute lung toxicity data of non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy in terms of dosimetric variables, location of dose within subvolumes of the lungs, and models of normal-tissue complication probability (NTCP)., Methods and Materials: Dose distributions of 49 non-small-cell lung cancer patients treated in a dose escalation protocol between 1992 and 1999 were analyzed (dose range: 57.6-81 Gy). Nine patients had RTOG Grade 3 or higher acute lung toxicity. Correlation with dosimetric and physical variables, as well as Lyman and parallel NTCP models, was assessed. Lungs were evaluated as a single structure, as superior and inferior halves (to assess significance of dose to upper and lower lungs), and as ipsilateral and contralateral lungs., Results: For the whole lung, Grade 3 or higher pneumonitis was significantly correlated (p 0.5 for superior lung indices, and >0.1 for contralateral lung indices studied)., Conclusions: For these patients, commonly used dosimetric and NTCP models are significantly correlated with >or= Grade 3 pneumonitis. Equivalently strong correlations are found in the lower portion of the lungs and the ipsilateral lung, but not in the upper portion or contralateral lung.

Purpose: To evaluate dosimetry of deep inspiration breath-hold (DIBH) relative to free breathing (FB) for three-dimensional conformal radiation therapy of lung cancer with 6-MV photons and Monte Carlo (MC) dose calculations., Methods and Materials: Static three-dimensional conformal radiation therapy, 6-MV plans, based on DIBH and FB CT images for five non-small-cell lung cancer patients, were generated on a clinical treatment planning system with equivalent path length tissue inhomogeneity correction. Margins of gross to planning target volume were not reduced for DIBH plans. Cord and lung toxicity determined the maximum treatment dose for each plan. Dose distributions were recalculated for the same beams with an MC dose calculation algorithm and electron density distributions derived from the CT images., Results: MC calculations showed decreased target coverage relative to treatment-planning system predictions. Lateral disequilibrium caused more degradation of target coverage for DIBH than for FB (approximately 4% worse than expected for FB vs. 8% for DIBH). However, with DIBH higher treatment doses could be delivered without violating normal tissue constraints, resulting in higher total doses to gross target volume and to >99% of planning target volume., Conclusions: If DIBH enables prescription dose increases exceeding 10%, MC calculations indicate that, despite lateral disequilibrium, higher doses will be delivered to medium-to-large, partly mediastinal gross target volumes, providing that 6-MV photons are used and margins are not reduced.

Purpose: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC., Methods and Materials: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied., Results: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test)., Conclusion: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.

Purpose: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients., Materials and Methods: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans., Results: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart., Conclusions: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.