Impact of toxicity grade and scoring system on the relationship between mean lung dose and risk of radiation pneumonitis in a large cohort of patients with non-small cell lung cancer.

PURPOSE: To compute the risk of radiation pneumonitis (RP) as a function of mean lung dose (MLD), with RP scored using three grading systems and analyzed at four threshold levels of toxicity in a large cohort of patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy (RT). METHODS AND MATERIALS: On the basis of medical records and radiographic images, RP was scored retrospectively in 442 patients with NSCLC who had >or=6 months of follow-up after the end of RT. The severity of RP was scored for each patient using the National Cancer Institute (NCI) Common Toxicity Criteria, version 2.0 (CTC2.0); the NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE3.0); and the grading system of the Radiation Therapy Oncology Group (RTOG). For each grading system and for each of four levels of toxicity (Grade >or=1, >or=2, >or=3, >or=4), the Lyman, logistic, and log-logistic normal tissue complication probability (NTCP) models were fitted to the data as functions of MLD. The parameter estimates from the model fits are listed in table form, and the RP risk estimates are presented graphically for the Lyman and log-logistic NTCP models. RESULTS: The results presented here illustrate the impact of scoring system and level of toxicity on the relationship between MLD and RP risk. CONCLUSIONS: These results facilitate quantitative comparisons between our data and studies of RP risk reported by others, and several examples of such comparisons are provided.

Pretreatment verification of IMSRT using electronic portal imaging and Monte Carlo calculations.

The use of an amorphous silicon electronic portal imaging device (EPID) and Monte Carlo calculations were investigated for pretreatment fluence verification in intensity modulated stereotactic radiotherapy (IMSRT). Monte Carlo calculations were performed using BEAM, a general purpose Monte Carlo code to simulate radiation beams from radiotherapy units. The dose distribution to the EPID phosphor was calculated by BEAM and then converted to pixel value using a pixel calibration curve. The calibration correlated calculated pixel dose to the measured pixel value for a range of open fields. Points within the region bounded by the photon jaws were extracted for comparison. Criteria for successful verification were 5% local percent difference in high dose regions, 1 mm distance to agreement in high gradient regions, or 2% of the Monte Carlo calculated central axis pixel value in low dose regions. Software was written to quantitatively compare the measured and calculated EPID images. Successful verification of the modulated field required that >or=95% of compared points fall within the comparison criteria. Dose response of the EPID was found to be linear with Monte Carlo calculated doses over the dose ranges examined in this work Comparison of the measured and calculated EPID dose distributions showed good agreement with 97% of the points passing criteria. The sensitivity of the methodology to detect field shaping errors was tested by introducing positioning errors in segments of the modulated field. These sensitivity tests indicate that the comparison software designed for this work can detect a 1 mm positioning error in a single segment of the composite IMSRT field. It should be noted, however, that the work presented here is a proof of concept and currently not a clinically viable QA tool. It represents a limited evaluation using a single IMSRT field, and verification of additional fields will be required for a comprehensive evaluation of the described methods before broad conclusions can be drawn. Additionally, the results of this work are subject to the comparison criteria that were used. Clinical implementation of the proposed technique should be evaluated for the specific institutional criteria where it will be employed.

Patterns of cardiac perfusion abnormalities after chemoradiotherapy in patients with lung cancer.

OBJECTIVE: We evaluated the prevalence of myocardial perfusion defects using myocardial perfusion imaging (MPI) after chemoradiation or radiation therapy (CRT/RT) in lung cancer patients and described their patterns in relation to tumor location. METHODS: MPI in 44 patients who received RT for lung cancer and 44 control patients were compared. The two groups were comparable in risk factors for coronary artery disease. Data regarding tumor stage and location, interval between CRT/RT and MPI, and mean radiation dose to the heart was collected. The level of radiation delivered to the affected segments of the left ventricle versus the normal segments was compared using the isodose lines on the simulation computed tomography. RESULTS: Considering all tumor locations, 8 patients (18%) demonstrated MPI defects after CRT/RT versus 9 (20%) in the controls. However, 7 of 18 patients (39%) with centrally located tumors in the CRT/RT group versus only 1 of 15 patients (7%) in the control group demonstrated MPI defect (p= 0.04). The defects in the CRT/RT group were in the anterior and septal segments while the defects were in different segments in the controls. The median interval between end of RT and MPI was 12.3 months. The affected segments in the CRT/RT group received a mean radiation dose of 39.6 versus 11.4 Gy (p = 0.003) to the normal segments. CONCLUSIONS: CRT/RT to centrally located lung tumors tends to cause anterior/septal MPI defects. Abnormal MPI segments in the CRT/RT group have received significantly higher radiation than normal segments.

Analysis of radiation pneumonitis risk using a generalized Lyman model.

PURPOSE: To introduce a version of the Lyman normal-tissue complication probability (NTCP) model adapted to incorporate censored time-to-toxicity data and clinical risk factors and to apply the generalized model to analysis of radiation pneumonitis (RP) risk. METHODS AND MATERIALS: Medical records and radiation treatment plans were reviewed retrospectively for 576 patients with non-small cell lung cancer treated with radiotherapy. The time to severe (Grade >/=3) RP was computed, with event times censored at last follow-up for patients not experiencing this endpoint. The censored time-to-toxicity data were analyzed using the standard and generalized Lyman models with patient smoking status taken into account. RESULTS: The generalized Lyman model with patient smoking status taken into account produced NTCP estimates up to 27 percentage points different from the model based on dose-volume factors alone. The generalized model also predicted that 8% of the expected cases of severe RP were unobserved because of censoring. The estimated volume parameter for lung was not significantly different from n = 1, corresponding to mean lung dose. CONCLUSIONS: NTCP models historically have been based solely on dose-volume effects and binary (yes/no) toxicity data. Our results demonstrate that inclusion of nondosimetric risk factors and censored time-to-event data can markedly affect outcome predictions made using NTCP models.

Lung perfusion imaging can risk stratify lung cancer patients for the development of pulmonary complications after chemoradiation.

INTRODUCTION: We investigated the value of lung perfusion imaging in predicting the risk of developing pulmonary complications after chemoradiation (CRT) or radiation therapy (RT) for lung cancer. METHODS: Fifty patients who underwent lung perfusion imaging before RT for lung cancer were included. Planar and single photon emission computed tomography/computed tomography images of the lungs were obtained. Lung perfusion score (LPS) was developed to visually grade localized perfusion defect per lung on a scale of 0 to 4 and perfusion pattern in the remaining lungs on a scale of 1 to 4. The LPS is the sum of the score for the localized perfusion defect in each lung plus the score for the remaining lungs perfusion. LPSs were correlated with pulmonary function tests and the patients were followed for 8 months after therapy to determine the incidence of grade 2 to 5 symptomatic therapy related pulmonary complications according to the common terminology criteria for adverse events (CTCAE 3.0). RESULTS: Thirty-four patients underwent CRT and 16 underwent RT. The mean total radiation dose delivered was 56.1 +/- 10.4 Gy. Eighteen patients (36%) suffered from pulmonary complications at a mean interval of 3.4 months after therapy. Nine patients had grade 2, 7 had grade 3, 1 had grade 4, and 1 had grade 5 pulmonary complications. The mean LPS was 4.9 in patients who developed pulmonary complications versus 3.5 in patients who did not (p = 0.01). There were no significant difference between pulmonary function tests in the patients with pulmonary complications and the patient without. In addition, there were no significant differences between the mean lung radiation dose, the volume of lung irradiated or the percentage of lung receiving greater than 20 Gy between the two groups. CONCLUSIONS: LPS using lung perfusion imaging is useful for predicting possible pulmonary complications after CRT or RT in lung cancer patients.

Underestimation of low-dose radiation in treatment planning of intensity-modulated radiotherapy.

PURPOSE: To investigate potential dose calculation errors in the low-dose regions and identify causes of such errors for intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: The IMRT treatment plans of 23 patients with lung cancer and mesothelioma were reviewed. Of these patients, 15 had severe pulmonary complications after radiotherapy. Two commercial treatment-planning systems (TPSs) and a Monte Carlo system were used to calculate and compare dose distributions and dose-volume parameters of the target volumes and critical structures. The effect of tissue heterogeneity, multileaf collimator (MLC) modeling, beam modeling, and other factors that could contribute to the differences in IMRT dose calculations were analyzed. RESULTS: In the commercial TPS-generated IMRT plans, dose calculation errors primarily occurred in the low-dose regions of IMRT plans (<50% of the radiation dose prescribed for the tumor). Although errors in the dose-volume histograms of the normal lung were small (<5%) above 10 Gy, underestimation of dose <10 Gy was found to be up to 25% in patients with mesothelioma or large target volumes. These errors were found to be caused by inadequate modeling of MLC transmission and leaf scatter in commercial TPSs. The degree of low-dose errors depends on the target volumes and the degree of intensity modulation. CONCLUSIONS: Secondary radiation from MLCs contributes a significant portion of low dose in IMRT plans. Dose underestimation could occur in conventional IMRT dose calculations if such low-dose radiation is not properly accounted for.

Association between systemic chemotherapy before chemoradiation and increased risk of treatment-related pneumonitis in esophageal cancer patients treated with definitive chemoradiotherapy.

BACKGROUND: There is limited information on risk factors for treatment-related pneumonitis in esophageal cancer patients. AIM OF THE STUDY: To determine factors associated with treatment-related pneumonitis in esophageal cancer patients treated with definitive chemoradiotherapy. MATERIALS AND METHODS: We retrospectively reviewed clinical data from esophageal cancer patients treated with definitive chemoradiotherapy from 2000 to 2003. Demographic, clinical, and treatment-related data were collected for all patients. The time to occurrence of grade > or =2 pneumonitis was calculated from the end of radiotherapy. Univariate analyses were performed to determine the existence of any association between patient demographic, clinical, or treatment characteristics and pneumonitis. RESULTS: In total, 96 patients were included in the study with a median follow-up of 8 months (range, <1-48 months). Among them, 23 patients also received an average of two cycles of systemic chemotherapy before the initiation of concurrent chemoradiation. The incidence of grade > or =2 pneumonitis was 22% at 1 year. Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade > or =2 pneumonitis (p = 0.003), with the 1-year incidence of grade > or =2 pneumonitis for patients with and without systemic chemotherapy being 49 and 14%, respectively. No other clinical or dosimetric factors investigated were associated with the risk of grade > or =2 pneumonitis. CONCLUSIONS: Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade > or =2 pneumonitis, suggesting that induction chemotherapy may have sensitized the lung tissue to radiation damage in esophageal cancer patients.

Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy.

PURPOSE: To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT). METHODS AND MATERIALS: Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose-volume histogram for the whole heart and pericardium. RESULTS: The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0-16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose-volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32-38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE. CONCLUSIONS: High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose-volume of the irradiated pericardium and heart.

Intrathoracic patterns of failure for non-small-cell lung cancer with positron-emission tomography/computed tomography-defined target delineation.

PURPOSE: Dosimetric studies suggested several advantages to defining the radiotherapy target by using positron-emission tomography (PET)/computed tomography (CT) compared with CT alone. We investigated patterns of treatment failure in patients treated to a PET-defined radiotherapy target and evaluated the effect of standardized uptake value (SUV) on recurrence after radiotherapy. METHODS AND MATERIALS: Thirty-five patients with non-small-cell lung cancer who underwent PET/CT simulation for definitive radiotherapy were included. The PET/CT scans were obtained with patients in the treatment position with custom immobilization for use in radiation treatment planning. Nine to 11 regions of interest (ROIs) were identified for each patient, including the primary tumor and regional nodes. Maximum SUV, volume, and mean dose received were recorded for each ROI, and follow-up scans were used to evaluate for recurrence in each ROI. RESULTS: We identified 353 ROIs from 35 patients; 5.7% of patients developed isolated out-of-field recurrences. Recursive partitioning analysis was used to divide ROIs into low, intermediate, and high risk by using volume and SUV. All low-risk ROIs with volumes less than 1.2 cm3 were recurrence free compared with 73% of intermediate-risk ROIs (volume >or=1.2 cm3; SUV 13.8). CONCLUSION: Limiting the target volume to predominantly PET-positive disease resulted in a low rate of isolated out-of-field recurrences. The SUV and volume were predictors of recurrence. Recursive partitioning analysis identified SUVs greater than 13.8 as the best identifier of ROIs at the greatest risk of recurrence; control rates for this subgroup did not show a dose-response relationship within the range of doses administered.

Variations in energy spectra and water-to-material stopping-power ratios in three-dimensional conformal and intensity-modulated photon fields.

Because of complex dose distributions and dose gradients that are created in three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), photon- and electron-energy spectra might change significantly with spatial locations and doses. This study examined variations in photon- and electron-energy spectra in 3D-CRT and IMRT photon fields. The effects of spectral variations on water-to-material stopping-power ratios used in Monte Carlo treatment planning systems and the responses of energy-dependent dosimeters, such as thermoluminescent dosimeters (TLDs) and radiographic films were further studied. The EGSnrc Monte Carlo code was used to simulate megavoltage 3D-CRT and IMRT photon fields. The photon- and electron-energy spectra were calculated in 3D water phantoms and anthropomorphic phantoms based on the fluence scored in voxel grids. We then obtained the water-to-material stopping-power ratios in the local voxels using the Spencer-Attix cavity theory. Changes in the responses of films and TLDs were estimated based on the calculated local energy spectra and published data on the dosimeter energy dependency. Results showed that the photon-energy spectra strongly depended on spatial positions and doses in both the 3D-CRT and IMRT fields. The relative fraction of low-energy photons (< 100 keV) increased inversely with the photon dose in low-dose regions of the fields. A similar but smaller effect was observed for electrons in the phantoms. The maximum variation of the water-to-material stopping-power ratio over the range of calculated dose for both 3D-CRT and IMRT was negligible (< 1.0%) for ICRU tissue, cortical bone, and soft bone and less than 3.6% for dry air and lung. Because of spectral softening at low doses, radiographic films in the phantoms could over-respond to dose by more than 30%, whereas the over-response of TLDs was less than 10%. Thus, spatial variations of the photon- and electron-energy spectra should be considered as important factors in 3D-CRT and IMRT dosimetry.

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.

Assessing respiration-induced tumor motion and internal target volume using four-dimensional computed tomography for radiotherapy of lung cancer.

PURPOSE: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. METHODS AND MATERIALS: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. RESULTS: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. CONCLUSIONS: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung.

Preserving functional lung using perfusion imaging and intensity-modulated radiation therapy for advanced-stage non-small cell lung cancer.

PURPOSE: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. RESULTS: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. CONCLUSION: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients.

Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy.

PURPOSE: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade > or = 3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. RESULTS: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade > or = 3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). CONCLUSIONS: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade > or = 3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

The prevalence of myocardial ischemia after concurrent chemoradiation therapy as detected by gated myocardial perfusion imaging in patients with esophageal cancer.

UNLABELLED: The detection of myocardial perfusion abnormalities after radiation therapy (RT) has been investigated previously in patients with lymphoma and breast cancer. However, the prevalence and association of such abnormalities with RT in esophageal cancer patients have not been investigated previously. METHODS: The prevalence of myocardial perfusion abnormalities detected using gated myocardial perfusion imaging (GMPI) in patients with esophageal cancer after RT (RT group) was compared with that in patients with esophageal cancer who did not undergo RT (NRT group). The patients' data were extracted from a prospectively collected database. The results of GMPI that were read by multiple readers were tested further by an expert reader who was unaware of the patients' clinical information. This reader's findings were correlated with the different RT isodose lines as seen in the CT for RT planning. Isodose lines containing the affected segments in GMPI as well as the rest of the left ventricle were recorded. Additionally, information with regard to the mean radiation dose to the heart for each patient was collected. An overall, mean radiation dose to the heart in patients with abnormal GMPI studies was compared with that in patients with normal GMPI studies. RESULTS: Fifty-one patients were included, 26 in the RT group and 25 in the NRT group. The mean and median interval between RT and GMPI was 7.5 and 3.0 mo, respectively. We identified myocardial perfusion defects in 14 patients (54%) in the RT group and in 4 patients (16%) in the NRT group. Eleven patients (42%) in the RT group had mild inferior wall ischemia versus only 1 patient (4%) in the NRT group (P = 0.001). All of the patients with inferior wall ischemia had distal esophageal cancer. The remaining 12 patients in the RT group and 21 patients in the NRT group had normal GMPI results. The mean left ventricular ejection fraction was 59.0% +/- 10.7% in the RT group and 59.3% +/- 9.8% in the NRT group (P = not significant). Good agreement was found between the GMPI results interpreted by multiple readers and those of the single expert reader (kappa = 0.84). In 7 of 10 patients (70%) who had abnormal GMPI results in the RT group, the myocardial perfusion defect was encompassed in RT isodose lines >/= 45 Gy, whereas in only 5 of 20 patients (25%) the normal left ventricle was included in the RT isodose line >/= 45 Gy. CONCLUSION: RT is associated with a high prevalence of inferior left ventricular ischemia, as detected using GMPI in patients with distal esophageal cancer. Most perfusion defects are encompassed within an isodose line >/= 45 Gy in the RT plan.

Dosimetric verification for intensity-modulated radiotherapy of thoracic cancers using experimental and Monte Carlo approaches.

PURPOSE: To investigate the dosimetric accuracy of commercial treatment planning systems used in intensity-modulated radiotherapy (IMRT) for thoracic cancer. METHODS AND MATERIALS: Clinical IMRT plans for lung and esophageal cancers and mesothelioma were used to investigate the accuracy of dose calculations from two commercial treatment planning systems (Pinnacle and Corvus systems). Dose distributions were measured with ion chambers and thermoluminescent dosimeters for individual IMRT fields and composite treatment plans in water phantoms and anthropomorphic phantoms. A Monte Carlo-based system was established to compute three-dimensional dose distributions to compare with the treatment planning system calculations. RESULTS: Dose calculations from the Pinnacle system were acceptable within 5% of the local dose or a 5-mm distance-to-agreement for 80% of the points measured with ion chambers, 74% of the points measured with thermoluminescent dosimeters, and 96% of the points compared with the Monte Carlo calculations. For the Corvus system, 89% of the points agreed with the measured dose and 98% agreed with the Monte Carlo calculations. Underestimation of the dose from the treatment planning system was found in the low-dose regions (<50% of the prescribed dose), possibly caused by inadequate modeling of the multileaf collimators. CONCLUSION: The Pinnacle and Corvus dose calculations were acceptable for thoracic IMRT in high-dose regions. Beam modeling is likely the most critical factor for the accuracy of IMRT dose calculations.

Dose-volume modeling of the risk of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.

PURPOSE: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. METHODS AND MATERIALS: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. RESULTS: Normal-tissue complication probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses > or = 5 Gy (VS5), that is, exposed to doses < 5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving > or = 5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, infinity), m = 0.55 (0.22, 1.02), and D50 = 17.5 Gy (9.4 Gy, 102 Gy). CONCLUSIONS: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving < 5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of the radiation dose distribution in the lung.

Development and commissioning of a multileaf collimator model in monte carlo dose calculations for intensity-modulated radiation therapy.

A multileaf collimator (MLC) model, "MATMLC," was developed to simulate MLCs for Monte Carlo (MC) dose calculations of intensity-modulated radiation therapy (IMRT). This model describes MLCs using matrices of regions, each of which can be independently defined for its material and geometry, allowing flexibility in simulating MLCs from various manufacturers. The free parameters relevant to the dose calculations with this MLC model included MLC leaf density, interleaf air gap, and leaf geometry. To commission the MLC model and its free parameters for the Varian Millennium MLC-120 (Varian Oncology Systems, Palo Alto, CA), we used the following leaf patterns: (1) MLC-blocked fields to test the effects of leaf transmission and leakage; (2) picket-fence fields to test the effects of the interleaf air gap and tongue-groove design; and (3) abutting-gap fields to test the effects of rounded leaf ends. Transmission ratios and intensity maps for these leaf patterns were calculated with various sets of modeling parameters to determine their dosimetric effects, sensitivities, and their optimal combinations to give the closest agreement with measured results. Upon commissioning the MLC model, we computed dose distributions for clinical IMRT plans using the MC system and verified the results with those from ion chamber and thermoluminescent dosimeter measurements in water phantoms and anthropomorphic phantoms. This study showed that the MLC transmission ratios were strongly dependent on both leaf density and the interleaf air gap. The effect of interleaf air gap and tongue-groove geometry can be determined most effectively through fence-type MLC patterns. Using the commissioned MLC model, we found that the calculated dose from the MC system agreed with the measured data within clinically acceptable criteria from low- to high-dose regions, showing that the model is acceptable for clinical applications.

Risk factors for acute esophagitis in non-small-cell lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy.

PURPOSE: To determine the risk factors for acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemotherapy (CCT) and three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Clinical data were retrospectively analyzed for 215 NSCLC patients treated with CCT and 3D-CRT during 2000-2003, 127 of whom also had induction chemotherapy (ICT). Carboplatin and paclitaxel were the most commonly used agents for both ICT and CCT. The median prescription dose of radiotherapy was 63.5 Gy in 35 fractions. AE was graded during each treatment week and 1-month follow-up visits. The factors related to clinical and disease characteristics, CCT and 3D-CRT treatments, and treatment planning were reviewed and analyzed for their association with Grade > or =3 AE using univariate and multivariate logistic tests. RESULTS: The rate of any grade AE was 93.0% and of Grade > or =3 was 20.5%. Univariate analyses showed that none of the clinical factors was significantly associated with Grade > or =3 AE. However, the mean radiation dose to the esophagus, the absolute esophageal volume treated above 15 Gy (aV15) through aV45 Gy, and the relative esophagus volume treated above 10 Gy (rV10) through rV45 Gy were significant risk factors for Grade > or =3 AE. Only rV20 was retained as the single risk factor in multivariate analyses. CONCLUSIONS: The risk of AE in the NSCLC patients treated with CCT and 3D-CRT was primarily determined by dosimetric factors. These factors should be carefully considered during treatment planning to minimize the incidence of AE.

Beam angle optimization and reduction for intensity-modulated radiation therapy of non-small-cell lung cancers.

PURPOSE: To optimize beam angles and reduce the number of beams used for intensity-modulated radiation therapy (IMRT) of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: An exhaustive search scheme was used to perform beam angle optimization (BAO) for IMRT of NSCLC. This approach involved intercomparison of all possible beam angle combinations and selection of the best angles based on the scores or costs of the objective functions used in the treatment plan optimization. Ten Stage III NSCLC cases were selected to evaluate the BAO algorithm and dosimetry benefits of IMRT-BAO. IMRT plans using five or seven coplanar beams were optimized and compared with those using nine equal-spaced beams. Results of BAO were also compared between plans using different numbers of beams with or without fluence modulation. RESULTS: Each anatomic structure, e.g., tumor or lung, had its own preferred beam angles. Thus, BAO required appropriate balance of competing objective functions. Plans using fewer angles (five or seven beams) could achieve plan quality similar to those using nine equal-spaced beams, however with reduced monitor units and field segments. The number of beams used for the treatment (five vs. seven) and the fluence modulation (open or IMRT beams) did not have a significant impact on the results of the BAO. CONCLUSIONS: Use of fewer beams (e.g., five) for lung IMRT could result in acceptable plan quality but improved treatment efficiency. A multiresolution search scheme could be developed for BAO using fewer and nonmodulated beams to reduce the computation cost of BAO.