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Background: Conformal external radiotherapy aims to improve tumor control by boosting tumor dose, reducing morbidity and sparing healthy tissues. To meet this objective careful visualization of the tumor and adjacent areas is required. However, one of the major issues to be solved in this context is the volumetric definition of the targets. This study proposes to compare the gross volume of lung tumors as delineated by specialized radiologists and radiotherapists of a cancer center. Methods: Chest CT scans of a total of 23 patients all with non-small cell lung cancer, not submitted to surgery, eligible and referred to conformal radiotherapy on the Hospital A. C. Camargo (São Paulo, Brazil), during the year 2004 were analyzed. All cases were delineated by 2 radiologists and 2 radiotherapists. Only the gross tumor volume and the enlarged lymph nodes were delineated. As such, four gross tumor volumes were achieved for each one of the 23 patients. Results: There was a significant positive correlation between the 2 measurements (among the radiotherapists, radiologists and intra-class) and there was randomness in the distribution of data within the constructed confidence interval. Conclusion: There were no significant differences in the definition of gross tumor volume between radiologists and radiotherapists. especially for those in advanced stage or for the inopera- Background Lung cancer is becoming increasingly frequent in both ble early-stage diseases. Conformal external radiotherapy genders worldwide. Three-dimensional conformal radio- is based on the extensive use of modern medical imaging therapy has been utilized for non-small-cell lung cancer, techniques, efficient dosimetric software, accurate patient Page 1 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 positioning methods, stringent verification and quality physicians due to imprecise tomographic data or diver- control of procedures, aiming to increase tumor control gent planning. These differences have already been by boosting tumor dose, reducing morbidity and sparing reported in literature for delineation of prostate, lungs, healthy tissues. Refined visualization of the tumor and central nervous system or esophagus tumors [9,17-23], adjacent areas is required to attain this objective. but the magnitude of all these differences is still not com- pletely assessed. Computerized planning has to calculate with accuracy and show the dose throughout the irradiated volume of The objective of this study is to compare the delineation the patient, taking into account the shape of the field and of gross tumor volume of lung tumors among experienced the modification devices of the beams used to obtain a radiologists and radiotherapists from an oncology refer- conformal and homogeneous dose in the target volume. ence center on Brazil. The idea of giving shape to the radiation fields, in order to shape only the target volume, is referred to as "target- Methods driven planning" and is the primary difference between Chest CT scans of all the patients with non-small-cell lung conformal (3D) and conventional (2D) radiotherapy. cancer, not submitted to surgery and referred to confor- Conformal radiotherapy permits better adaptation of the mal radiotherapy of Hospital A. C. Camargo (São Paulo, dosimetric distribution to the tumor volume, reduction of Brazil) during the year 2004 were analyzed. healthy organs exposure, and on the long term, higher dose of tumor irradiation [1-5]. All the tomographic exams were performed in the ade- quate position for treatment in the same tomography The volume of the tumor mass (gross tumor volume) rep- equipment (GE HiSPEED), with identical acquisition resents the area of greatest concentration of tumor cells. It parameters and injection of endovenous contrast is usually defined as the tumor clinically evident and visi- medium. Each acquisition was carried out in patients with ble in imaging studies, such as computed tomography or apnea, in the helicoidal mode, with pitch of 1 and slice magnetic resonance. The appropriate use of the imaging thickness of 7 mm reconstructed every 5 mm. study is crucial upon definition of tumor volume. A total group of 23 patients was analyzed, of which 9 were In the majority of cases, toxicities of degrees 3 to 5 are females and 14 males. The average age was 69 years, rang- lower than 10% in patients tested with higher doses, using ing from 53 to 85 years. At the time of the diagnosis, 5 three-dimensional conformal radiation therapy tech- were in clinical stage IB; 5, in IIB; 6, in IIIA; 6, in IIIB; and niques [6-8]. 1, in IV. However, one of the most difficult problems to solve in The 23 cases were delineated by two radiologists and two this context is the volumetric definition of targets [5,9,10]. radiotherapists from Hospital A. C. Camargo. The high precision of this radiotherapic technique demands a stringent and qualified approach by means of Each physician has received a written summary of the therapeutic preparation procedures [11,12]. Methodolog- medical records of each patient. Only the gross tumor vol- ical rules should be established for volumetric definition ume (i.e., the visible primary tumor and the enlarged of targets, taking into account the difficulties in delineat- lymph nodes) was delineated. According to definitions of ing the macroscopic volume of the target and its micro- the International Commission on Radiation Units and scopic involvement [5,13-15]. Measurements-ICRU (1993, 1999) the gross tumor vol- ume is the visible or palpable tumor extension. As regards Delineation is generally performed in many centers by lymph nodes, those whose smaller axis diameter is larger radiotherapists who often have no training or experience than or equal to 1 cm are considered compromised. The in radiology, making it harder to accurately identify the lymph nodes were included in the delineation of the gross details of anatomic structures in computed tomography tumor volume, when located close to the primary tumor, imaging. With the more generalized use of conformal or were delineated separately, if distant. We analyzed the radiotherapy and other new technologies, the immediate gross tumor volume as a whole: both the primary tumor need of assuring the quality control in the definition of and the enlarged lymph nodes in each section. The opti- gross tumor volume was evidenced . mal visualization parameters were defined in a prior study, with -600/1600 UH for the pulmonary window On the other hand, although radiologists are better quali- and +20/400 for the mediastinal window considered fied to interpret radiological anatomy, they are not always mandatory for delineation . The magnification factor familiar with the natural history of the disease. Differ- was chosen by the physician. The previous delineation ences in delineation can, therefore, be observed among was recorded, but was not made available to the other Page 2 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 physicians. For gross tumor volume calculation, delinea- correlation coefficient, in which we observe significant tion was performed with the ECLIPSE software from and positive correlation between the two measurements. VARIAN with the electronic cursor in each tomographic The intraclass correlation coefficient is equal to 0.762 (p < section, being thus the tumor area multiplied by the slice 0.001) with confidence interval of 95% equal to (0.522; thickness, and the total volume resulted from the sum of 0.891). the tumor volume of all slices. In this manner, we obtained 4 gross tumor volumes for each one of the 23 We can also evaluate this congruity by the Bland-Altman patients. method. Figure 4 shows the graph representing this anal- ysis. The differences between the measurements ranged The measurements were initially analyzed descriptively by from -466.27 to 26.23 with average of -31.35 and stand- means of the averages calculation, as well as the standard ard deviation of 101.27, thus we obtained a confidence deviations and medians and the observation of minimum interval of 95% equal to (-233.88; 171.18). and maximum values. Analyzing radiotherapists and radiologists findings, we The statistical methods utilized were Pearson's correlation utilized the average between the measurements of the coefficient, the Bland-Altman plot, the intraclass correla- radiologists and the average of the measurements of the tion coefficient described by Fleiss and the coefficient of radiotherapists. variation. The level of significance utilized for the tests was 5%. Figure 5 represents the measurements of the radiologists and of the radiotherapists and the value of Pearson's cor- relation coefficient, in which we observe significant and Results Table 1 shows the average, standard deviation, median, positive correlation between the two measurements. The minimum and maximum values observed by the radiolo- intraclass correlation coefficient is equal to 0.942 (p < gists and radiotherapists. 0.001) with confidence interval of 95% equal to (0.869; 0.975). Hence an excellent correlation between the two Analyzing the measurements of the radiotherapists, we measurements has been found. can see represented in figure 1, the two measurements of the radiotherapists and the value of Pearson's correlation We can also evaluate this congruity by the Bland-Altman coefficient, in which we observe significant and positive method. The graph representing this analysis is contained correlation between the two measurements. The intraclass in figure 6. The differences between the measurements correlation coefficient for the radiotherapist is 0.989 (p < ranged from -192.09 to 50.14 with average of -3.51 and 0.001) with confidence interval of 95% equal to (0.974; standard deviation of 48.73, thus we obtained a confi- 0.995). dence interval of 95% equal to (-100.98; 93.95). We can also evaluate this concordance by the Bland-Alt- In table 2, we calculate the coefficient of variation among man method. The graph representing this analysis is the 4 measurements, to wit: those of the 2 radiotherapists showed in Figure 2. The differences between the measure- and those of the 2 radiologists, which once again indicates ments ranged from 42.88 to 37.74, with average of 3.10 good congruity among them, with the exception of only and standard deviation of 21.15. Thus we obtained a con- one value. fidence interval of 95% equal to (-39.20; 45.41). Discussion Analyzing the radiologists' findings, Figure 3 shows the Inoperable lung cancer prognosis remains very poor. measurements they attained and the value of Pearson's Besides the alternate fractionated schemes and combined Table 1: Values of average, standard deviation, median, minimum and maximum of the values observed by the radiologists and radiotherapists Observer Average SD Median Minimum Maximum Radiotherapist 1 140.84 136.29 83.56 13.03 516.85 Radiotherapist 2 137.74 141.68 78.81 11.22 496.39 Average 139.29 138.61 74.44 12.13 496.26 Radiologist 1 127.13 128.03 72.36 13.87 450.26 Radiologist 2 158.48 169.21 65.36 12.09 547.91 Average 142.80 141.24 68.27 12.98 465.35 Page 3 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 Measurements so Figure 1 n's correlatioof n coefficient the radiotherapists and the value of Pear- Me correlat Figure 3 asurements o ion coefficients f the radiologists and the value of Pearson's Measurements of the radiotherapists and the value of Measurements of the radiologists and the value of Pearson's correlation coefficient. Pearson's correlation coefficients. therapies, new planning strategies, including conformal in thoracic radiotherapy could result in greater volume radiotherapy and dose increase, are under investigation variations [22,27,31,32], focused on the definition of [25-29]. lung cancer gross tumor volume as part of a delineation protocol. The three authors concluded that there is signif- It is known that the general survival rate, cause-specific icant variation in target volume definition. survival and local tumor control are directly correlated with the gross tumor volume in cm3. In the multivariate VAN DE STEENE et al. (2002), showed unexpected major analysis the most predictive independent survival variable interobservers' variability, with tumor delineation varying is the gross tumor volume . by several centimeters, due to: Recently, the data mentioned by LEUNENS et al. (1993), 1) difficulty in discriminating between tumor and atel- evidenced that the gross tumor volume definition is not ectasia; that simple, and there can be risks in excessive confidence in the medical capacity to estimate the tumor extension 2) difficulty in distinguishing normal and pathological with the imaging approaches . structures of the tumor; Due to the number of uncertainties and of phenomena 3) use of different tomographic windows and partial vol- related to the tumor, the definition of gross tumor volume ume effects; Measurements of Bland-Altman method Figure 2 the radiotherapists and the graph by the Me Altman method Figure 4 asurements of the radiologists and the graph by the Bland- Measurements of the radiotherapists and the graph Measurements of the radiologists and the graph by by the Bland-Altman method. the Bland-Altman method. Page 4 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 and SYMONDS (2002) suggest a compulsory period of structured training in section imaging diagnosis for radio- therapists . According to the recommendations of ICRU 50 (1991, 1993) and later on, of ICRU 62 (1999), gross tumor vol- ume delineation should be performed as close as possible to the tumor and/or lymph node, without adding any safety margin [37-39]. Successive additional volumes are designated taking into account other treatment uncertain- ties. A second attitude adopted by the majority consists of attempting to distinguish between the tumor tissue and the surrounding collapsed parenchyma. This choice calls for perfect tomographic acquisition with rapid injection M th Figure 5 e e value of Pearson's asurements of the radi correlation coefficient otherapists and the radiologists and of the contrast medium and a first series of slices per- Measurements of the radiotherapists and the radiol- formed immediately after the injection . ogists and the value of Pearson's correlation coeffi- cient. Our results were incompatible with those of VAN DE STEENE et al. (1996), SENAN et al. (1999) and GIRAUD et al. (2002), which exhibited significant differences in 4) insufficient anatomic knowledge . lung tumor delineation [22,34,40]. Another study carried out by GIRAUD et al. (2002) that In our study there was excellent intraclass correlation compared the delineation of gross tumor volume per- (Pearson's correlation coefficient) in the case of the radio- formed by radiologists and radiotherapists, showed sig- therapists and good correlation in the case of the radiolo- nificant differences between the two groups: radiologists gists. In the latter, the correlation was slightly lower due to tended to delineate lower and more homogeneous vol- a single point at which there was greater discrepancy umes than radiotherapists, especially in the "difficult" between the first and the second measurement. In the cases . The delineation of the target volume and high- analysis of radiotherapists and radiologists, we also risk organ constitutes a critical stage in conformal radio- observed excellent correlation between the two measure- therapy [5,9,10,13,35] and the subsequent steps are ments. dependent on correct gross-volume delineation. Field shaping and dose planning are based exclusively on the Congruity was also evaluated by the Bland-Altman tumor volumes and critical normal tissue delineated. method, while randomness was observed in the distribu- GIRAUD et al. (2002) suggested that the correct definition tion of data within the constructed confidence interval, of the gross tumor volume can be attained, when radio- and only one point fell outside the interval, indicating therapists are well trained in chest imaging . SUNDAR that the error among the measurements does not tend to increase when the measurement values are higher. More- over, the average of the differences was close to zero, indi- cating good concordance between the two measurements. The discrepant measurement of gross tumor volume of one of the radiologists resulted from associated atelectasis that constitutes the main cause of error in tumor volume delineation. We emphasize that in our study, we observed one case of tumor with mediastinal invasion, two with invasion of the thoracic wall and two causing lung atel- ectasis. Some peculiarities of Hospital A. C. Camargo might have contributed to these results, such as integration of the radiotherapy and diagnostic imaging departments, intern- M th Figure 6 e e graph asuremby the Bland-A ents of the radilothe tman method rapists and the radiologists and ship of the radiotherapy residents in diagnostic imaging Measurements of the radiotherapists and the radiol- ogists and the graph by the Bland-Altman method. with learning of sectional anatomy, and geographical proximity of the radiology and radiotherapy departments, Page 5 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 Table 2: Coefficient of variation (COV) among the 4 measurements (2 radiologists and 2 radiotherapists) Patient Radiotherapist 1 Radiotherapist 2 Radiologist 1 Radiologist 2 Average COV 1 108.55 127.42 127.29 155.28 129.64 0.15 2 369.29 370.13 391.36 387.46 379.56 0.03 3 125.05 121.29 125.97 130.56 125.72 0.03 4 13.03 11.22 13.87 12.09 12.55 0.09 5 52.13 33.13 35.87 27.78 37.23 0.28 6 68.45 78.81 72.54 65.36 71.29 0.08 7 83.56 65.31 72.36 64.18 71.35 0.12 8 35.90 27.40 46.20 27.02 34.13 0.26 9 77.58 49.27 67.62 41.39 58.97 0.28 10 135.91 109.46 81.64 547.91 218.73 1.01 11 65.30 65.82 83.64 116.94 82.93 0.29 12 186.47 199.94 178.92 317.77 220.78 0.30 13 453.51 496.39 382.78 466.78 449.87 0.11 14 33.94 32.31 28.72 28.98 30.99 0.08 15 195.41 215.96 157.15 172.20 185.18 0.14 16 71.31 62.83 64.20 67.13 66.37 0.06 17 53.26 52.13 52.19 51.76 52.34 0.01 18 516.85 475.67 450.26 480.44 480.81 0.06 19 266.67 302.54 303.24 308.28 295.18 0.06 20 95.41 94.10 50.23 46.40 71.54 0.38 21 121.23 83.49 59.19 56.56 80.12 0.37 22 73.29 53.71 43.71 47.11 54.46 0.24 23 37.24 39.65 34.97 25.58 34.36 0.18 which are located in the same building, on adjacent consistent delineation of target volumes is needed to floors. improve treatment and avoid complications. Although some authors have found large rates of interobserver vari- Despite of there are no statistically significant differences ability on volume delineation for lung cancer, in this sur- in the definition of gross tumor volume between radiolo- vey, there was no statistically significant difference in the gists and radiotherapists in this study, in nine of twenty- definition of gross tumor volume between radiotherapists three evaluated patients there was a difference greater than and radiologists or intraclasses. Some institutional charac- 20%, which can be clinically relevant. Most of these cases teristics should be responsible for this finding, such as involved primary tumors located close to the mediasti- integration between radiotherapy and diagnostic imaging num or chest wall, which hindered the proper measure- departments. ment of the lesions. Regardless of the overlapping volumes have not been assessed, in neither case the Competing interests observers considered different structures to delineate the The authors declare that they have no competing interests. target volumes. Authors' contributions Recently some authors have shown that delineation accu- CJT conceived of the study, and participated in its design, racy can be improved by using fluorodeoxyglucose-posi- acquisition, analysis and interpretation of data, and tron emission tomography (FDG-PET)/CT information. helped to draft the manuscript. FDG-PET/CT is a functional study that has proved to be more accurate than CT in determining extent of non- RC and PEN conceived of the study, and participated in its small-cell lung cancer. Integration of FDG-PET/CT on the design and coordination, and helped to draft the manu- volume delineation can reduce interobserver variation script. compared with CT based delineation and alter gross tumor volume in about 50% of the cases. [41,42] FDG- PNVP, RCF and DGC conceived of the study, and partici- PET/CT images are particularly useful in defining the tar- pated in its design, acquisition of data, and helped to draft get volume in the presence of atelectasis and in defining the manuscript. involved lymph nodes.  MAB and AGVB have been involved in literature review, Conclusion drafting the manuscript and revising it critically for publi- Radiotheraphy plays an important role in the manage- cation. ment of inoperable lung cancer patients, A precise and Page 6 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:28 http://www.ro-journal.com/content/4/1/28 defining the planning target volume in the irradiation of All authors have given final approval of the version to be prostate and seminal vesicles. Radiother Oncol 1998, 47:293-6. published. 20. 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