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1 Department of Radiology, Division of Diagnostic Imaging, The University of
Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX
77030.
2 Division of Radiation Oncology, The University of Texas M. D. Anderson Cancer
Center, Houston, TX 77030.
Received September 18, 2001;
accepted after revision December 27, 2001.
Presented at the annual meeting of the American Roentgen Ray Society,
Seattle, April-May 2001.
Abstract
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MATERIALS AND METHODS. Over a 36-month period, the chest CT scans of 19 patients with non-small cell lung cancer who were treated with 3D CRT were reviewed. CT scans were evaluated for findings of radiation injury (ground-glass opacities, consolidation, bronchiectasis, and volume loss). The presence, extent, and distribution of these findings were reached by consensus.
RESULTS. Radiation pneumonitis limited to a small area immediately around the tumor was present in all patients who were imaged within 3 months after completion of the treatment (n = 7). Radiation-induced fibrosis occurred in all patients (n = 19). Three distinct patterns of fibrosis were consistently present, and these were classified as modified conventional, masslike, and scarlike. Modified conventional fibrosis (consolidation, volume loss, and bronchiectasis similar to, but less extensive than, conventional radiation fibrosis) was seen in five patients. Masslike fibrosis (focal consolidation with traction bronchiectasis limited to the site of the original tumor) was seen in eight patients. Scarlike fibrosis (linear opacity in the region of the original tumor associated with moderate to severe volume loss) was seen in six patients.
CONCLUSION. Three-dimensional conformal radiation therapy results in three patterns of radiation fibrosis that differ from the conventional radiation-induced lung injury. Knowledge of the full spectrum of these manifestations is useful in the correct interpretation of CT scans after 3D CRT.
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Treatment planning for radiation therapy was performed by immobilizing patients in a Vac-Lok immobilization system (Med-Tec, Orange City, IA) on the CT scanner with their arms above their heads. Helical CT scans were obtained from the level of the cricoid cartilage to the bottom of the diaphragm using a 3- to 5-mm collimation. Gross tumor volume was determined by outlining the margins of the visible tumor. The clinical target volume accounts for microscopic tumor infiltration and was determined by adding a 5-mm expansion around the gross tumor volume. In patients with stage I or stage II disease, the clinical tumor volume was a simple expansion around the primary tumor and any enlarged hilar lymph nodes. Patients with a higher stage disease had their entire mediastinum irradiated to at least 45 Gy. The planning target volume, which is the volume that receives the radiation treatment, included an additional 1- to 2-cm uniform expansion around the clinical tumor volume to account for tumor motion and daily set-up variation.
Conformal radiation therapy was performed using multiple coplanar (oriented in the same axial plane as the tumor) or noncoplanar (orientated in axial and nonaxial planes to the tumor) radiation fields. Of the 19 patients, 18 received a total radiation dose ranging from 70.0 to 90.3 Gy given over 33-42 fractions. The total treatment time was between 44 and 61 days. Only one of these 18 patients had chemotherapy (which was completed 2 months before the beginning of radiotherapy). The 19th patient received concurrent chemotherapy and radiation with a radiation dose of 69.6 Gy in 58 fractions.
A total of 89 CT scans were obtained consisting of 19 baseline and 70 follow-up studies. Seventy-two of the CT scans were obtained at our institution using HiSpeed Advantage, HiLight Advantage, HiSpeed CT/i, and LightSpeed QX/i CT scanners (General Electric Medical Systems, Milwaukee, WI), and IV contrast material. Other institutions at which CT scans were obtained used scanners from various vendors (HiSpeed Advantage, HiLight Advantage, and HiSpeed CT/i [General Electric Medical Systems]; and Somatom HiQ [Siemens Medical Systems, Iselin, NJ]), and the CT examinations were performed with and without IV contrast material. Slice thickness was 7.0-7.5 mm with a pitch ranging from 1.0 to 1.5 on helical CT scans and 10 mm on nonhelical CT scans.
The average time interval between baseline CT and the beginning of radiation therapy was 30 days (range, 12-70 days). The mean interval between completion of therapy and the first CT evaluation was 4.5 months (range, 1-11 months). Seven of these patients underwent the first follow-up CT within 3 months, with an average of 1.7 months (range, 1-3 months). The mean interval between completion of radiotherapy and the last follow-up CT examination was 19 months (range, 5-37 months). An average of 4.6 follow-up CT scans (range, 1-9 scans) were obtained per patient.
All CT scans were reviewed by four fellowship-trained thoracic radiologists. The presence of abnormalities and the categorization of findings were reached by consensus. The CT scans were evaluated for findings of radiation pneumonitis (ground-glass opacities), radiation fibrosis (consolidation, bronchiectasis, and volume loss), and pleural effusions. The pretreatment CT served as a baseline for comparison.
Of the 19 patients, eight had squamous cell carcinoma, six had adenocarcinoma, four had poorly differentiated carcinoma, and one had adenoid cystic carcinoma. Six patients were stage IA, eight were stage IB, three were stage IIIA, and one was stage IIIB. One patient with previous pneumonectomy had metastatic tumor of the opposite lung that was considered stage IV. The patients with tumor stages IA and IB had contraindications to surgery. Seven tumors were located in the left upper lobe, four were in the left lower lobe, six were in the right upper lobe, and one each was in the middle lobe and right lower lobe. The average size of the tumor before treatment was 3.4 cm (range, 1.5-7.0 cm).
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In contrast to conventional radiotherapy treatment planning, 3D CRT planning uses a 3D image reconstructed from CT scanning data to determine the target volumes to be treated. A computer planning system is used to design beam arrangements with a variety of orientations that deliver maximal radiation dose to the tumor while limiting exposure to normal structures. Opposed beams are often not used, and the dose per field per day is usually below 2 Gy. Generally, multiple static coplanar and noncoplanar radiation fields are used, sometimes in unusual orientations (Fig. 1A). The beam arrangements are optimized to shape the dose distribution to the tumor's 3D configuration and to decrease exposure to the surrounding normal structures (Figs. 1B, 1C, and 1D). Also, the total exposure is distributed among the multiple radiation beams so that the normal lung in the path of the radiation beams is exposed to subtherapeutic doses. The results of the 3D CRT technique are a reduction in side effects and an increase in treatment dose to the tumor that should lead to better local tumor control [2,3,4,5], although the effects on overall survival are not yet clear [6].
Radiation changes in the lung after conventional radiotherapy have been well described by Libshitz et al. [7,8,9] and Ikezoe et al. [10,11] and are typically not evident on chest radiographs when the dosage is less than 30 Gy. Radiation injury of the lung is classified as early and late. The early phase (radiation pneumonitis) consists of cellular infiltration that is predominantly composed of macrophages and manifests radiologically as ground-glass opacities. Radiation pneumonitis is generally most prominent at 3-4 months after completion of radiotherapy. The later phase (radiation fibrosis) is marked by collagen deposition and fibrosis and manifests radiologically as volume loss, consolidation, and traction bronchiectasis. Radiation fibrosis is usually well established and stable at 12 months [7].
In our study population, CT findings of radiation pneumonitis were limited to the area immediately surrounding the tumor. Tada et al. [12] reported high-resolution CT findings of pneumonitis in both lungs of a patient after 3D CRT. Clinical pneumonitis in previous 3D CRT studies has been correlated with pulmonary function tests and the amount of lung irradiated [1, 5, 13]. However, the radiographic changes of pneumonitis from 3D CRT have not been well described. Our study did not show pneumonitis outside the area around the tumor, but our study is limited because of the small number of patients (n = 7) who received early CT follow-up. Also, high-resolution CT, which could show subtle changes of early pneumonitis, was not performed. Further studies using these techniques are needed for a more complete radiographic assessment.
Radiologic manifestations of radiation-induced fibrosis similar to conventional therapy (consolidation, volume loss, and traction bronchiectasis) occurred in 13 patients. However, because 3D CRT delivers a focused therapeutic dose to the tumor via multiple beams of 20 Gy or less, differences existed in the extent and distribution of these findings. In five patients, the fibrosis did not extend entirely from the anterior to the posterior pleural surface as is commonly seen in fibrosis from conventional treatment. Because this appearance closely resembled the pattern of conventional radiation fibrosis, this region of fibrosis was classified as the modified conventional pattern. In eight patients, consolidation and traction bronchiectasis were confined to a 2-cm region surrounding the original tumor. This region of fibrosis correlated with the maximal isodose curves of radiation delivery, resulting in a masslike area that was larger than the original tumor and was classified as a masslike pattern.
In the remaining six patients, the findings were markedly different from conventional radiation fibrosis. At the site of the tumor, only a small linear opacity less than 1 cm in width remained. The appearance was typical of a linear scar, and this finding was thus categorized as a scarlike pattern. The patients had complete or almost complete resolution of the tumor mass in this pattern. Clinical and radiologic reassessment of all patients in the study group is still being performed, and whether this more complete pattern of radiologic response is indicative of improved local control or survival is uncertain. However, currently, all patients with the scarlike fibrosis have had no recurrence of tumor.
Follow-up CT scans that have been obtained before radiation fibrosis has fully evolved can result in findings that are difficult to differentiate from recurrent tumor. Differentiation of evolving radiation fibrosis from recurrent tumor can be particularly difficult when the masslike pattern occurs. Follow-up CT scans have shown a stable or decreased size of the radiation fibrosis in the masslike pattern as the consolidation and bronchiectasis become more organized. The two patients excluded from this study had a masslike pattern that increased in size. Both patients were histologically proven to have tumor recurrence. Although tumor recurrence was seen in only two patients, it is expected from our experience with patients who undergo conventional radiotherapy that an increase in size of the radiation change in 3D CRT will indicate tumor progression.
Our study has limitations that could impact our findings. This study was retrospective, and the sample size was limited. Although the three patterns were relatively equal in occurrence, a larger sample size might reveal a predominant pattern. Although most patients had a follow-up of 12 months or more, a longer follow-up of all patients would be useful. It would also be beneficial to have an early follow-up of less than 3 months in all patients to make stronger conclusions about the development of radiation pneumonitis. In addition, the amount of radiation dosage that the patients received varied between 69.6 and 90.3 Gy. Patients involved in this study also had a variety of tumor histologies and disease stages. Although the three patterns of CT fibrosis do not appear to be related to the dosage, histology, or stage of disease, larger studies are needed for definitive correlation.
In conclusion, the appearance and evolution of radiation fibrosis after 3D CRT for non—small cell lung cancer differ from fibrosis occurring after conventional radiotherapy. In our study, radiologic manifestations of 3D CRT differed in extent, distribution, and appearance. Three main patterns were identified: modified conventional, masslike, and scarlike. Approximately 40% of the patients had masslike fibrosis that potentially could have been misinterpreted as progressive neoplastic disease. Because 3D CRT is becoming a common method of treating lung cancer, knowledge of the full spectrum of radiologic manifestations of 3D CRT can be useful in preventing diagnostic errors.
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