Strahlentherapie und Onkologie Original Article

Thermoplastic Patient Fixation Influence on Chest Wall and Target Motion during Radiotherapy of Lung Cancer

Arpad Kovacs1, Janaki Hadjiev1, Ferenc Lakosi1, Marta Vallyon1, Zsolt Cselik1, Peter Bogner1, Akos Horvath2, Imre Repa1

Background and Purpose: Several methods have been developed to reduce tumor motions and patient movements during radio-therapy of lung cancer. In this study, a multislice CT-based analysis was performed to examine the effect of a thermoplastic pa-tient immobilization system on the chest wall and tumor motions. Patients and Methods: Ten patients with stage II–IV lung cancer were enrolled into the study. According to tumor localization, five patients had peripheral, and five patients central lung cancer (T2–T4). In total, six series of measurements were made with a multislice CT scanner, both with and without mask fixation, in normal breathing, at maximal tidal volume inhalation, and at maximal tidal volume exhalation. Results: Movements of chest wall, diaphragm and tumor, with and without mask, under different breathing conditions were registered. With the use of the immobilization system, no significant difference was found in diaphragmatic movements (mean deviation of diaphragm: 41.7–40.5 mm to the right, and 40.5–36.8 mm to the left side) and in tumor motions (mean deviation of tumor: 15.3–12.4 mm in craniocaudal, and 11.5–8.8 mm in posterolateral direction, mean medial deviation: 4.6–4.1 mm, mean lateral deviation: 7.2–5 mm). Significant differences were observed concerning tumor motions in anteroposterior direction (mean: 8.9–6.3 mm) and transverse chest movements in anteroposterior direction. Conclusion: Besides the advantage of optimal patient positioning, the movements of the bony chest wall can be considerably reduced by using the immobilization system. However, this fixation system has limitations concerning its suitability for minimiz-ing tumor motions.

Key Words: Lung cancer · Mask fixation · Multislice CT · Tumor motion

Strahlenther Onkol 2007;183:271–8 DOI 10.1007/s00066-007-1681-6

Thermoplastisches Patientenimmobilisierungssystem. Einfluss auf Thoraxwand- und Tumorbewegung bei der Strahlentherapie des Lungenkarzinoms

Hintergrund und Ziel: Zahlreiche Methoden wurden entwickelt, um die Tumor- und Patientenbewegungen während der Strahlen-therapie von Lungenkarzinomen zu reduzieren. In dieser Studie wurde eine Mehrschicht-CT-basierte Analyse zur Untersuchung der Auswirkungen eines thermoplastischen Patientenimmobilisierungssystems auf die Thoraxwand- und Tumorbewegungen durch-geführt. Patienten und Methodik: Zehn Patienten mit Lungenkrebs Stadium II–IV wurden in die Studie eingeschlossen. Gemäß der Tu-morlokalisation wiesen fünf Patienten ein peripheres und fünf Patienten ein zentrales Lungenkarzinom auf (T2–T4). Insgesamt wurden sechs Messserien mit einem Mehrschicht-CT-Scanner durchgeführt: mit und ohne Maskenfixierung, bei normaler Atmung sowie mit maximalem Atemvolumen bei Ein- und Ausatmung. Ergebnisse: Die Brustwand-, Zwerchfell- und Tumorbewegungen wurden mit und ohne Maske bei unterschiedlichen Atmungszu-ständen registriert. Bei Verwendung des Immobilisierungssystems wurden keine signifikanten Unterschiede in den Zwerchfellbe-wegungen (durchschnittliche Abweichung des Diaphragmas: 41,7–40,5 mm nach links und 40,5–36,8 mm nach rechts) und den Tumorbewegungen (durchschnittliche Abweichung des Tumors: 15,3–12,4 mm in kraniokaudaler und 11,5–8,8 mm in postero-anteriorer Richtung, durchschnittliche mediale Abweichung: 4,6–4,1 mm, durchschnittliche laterale Abweichung 7,2–5 mm)

Received: September 15, 2006; accepted: March 5, 2007

1 Health Science Center, University of Kaposvar, Hungary, 2 Department of Radiotherapy, Medical and Health Science Center, University of Debrecen, Hungary.

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Introduction Nowadays, lung cancer is the leading cause of cancer death, both in the female and male population [6]. In the treatment of the disease, surgery, radiotherapy and chemotherapy play an important role [1, 4, 9, 10]. Radiotherapy and chemothera-py are often used as a combined modality, like in a variety of different tumors [5, 19, 38].

In the past years, as three-dimensional conformal irradia-tion therapy has come into general use, the question of patient positioning, examination of tumor motions and definition of planning target volume (PTV), clinical target volume (CTV) and gross tumor volume (GTV) became of more prevailing importance [23, 37].

To date, the definition of target volume to be treated with three-dimensional conformal irradiation is most usually performed on the basis of CT images [17]. Due to the lack of exact knowledge of tumor motions arising from breathing, a larger irradiation volume is necessary, and subsequently, more normal tissues will be damaged during treatment [2, 8, 18, 25]. According to International Commission on Radiation Units and Measurements (ICRU) Report, Recommendation No. 62, the PTV has to include the uncertainties arising from internal organ motion, patient movements and positioning errors [14].

The aim of our study was to analyze the effects of our patient-positioning system on the chest wall and tumor mo-

tions under extreme breathing conditions using multislice CT.

Patients and Methods A total of ten patients with lung cancer were enrolled in-to the study. For patient selection, the essential criteria in-cluded good performance status of the patients (ECOG 0–1), appropriate respiratory parameters, and a good com-pliance. Eight men and two women with a mean age of 60.6 years (43–74 years) participated in the study. Five pa-tients were diagnosed with central, and five with peripheral tumor. Three patients had microcellular, and seven non-small cell lung carcinoma. As part of their complex treat-ment, five patients received chemotherapy as well (Table 1). All patients were informed about the examination and asked for written consent accepted by the local ethics com-mittee.

For patient positioning we used the thermoplastic mask fixation system combined with arm support, applied at our institute in daily routine work (Figure 1). The arm support in-cluded three hand holders and a shoulder rest. The individual thermoplastic masks were stabilized by four cuts on the mask-fixing board.

Before the examination patients were placed on the central part of the board (under laser-assisted positioning and attending to keep the body straight), hanging with both

festgestellt. Signifikante Unterschiede waren bezüglich der Tumorbewegungen in anteroposteriorer Richtung (durchschnittlich 8,9–6,3 mm) und der transversalen Brustkorbbewegungen in anteroposteriorer Richtung zu beobachten. Schlussfolgerung: Neben dem Vorteil einer optimalen Patientenpositionierung können die Bewegungen der Thoraxwand mit Hilfe des Immobilisierungssystems erheblich reduziert werden. Dieses Fixierungssystem hat jedoch auch Grenzen hinsichtlich seiner Eignung zur Minimierung der Tumorbewegungen.

Schlüsselwörter: Lungenkarzinom · Maskenfixierung · Mehrschicht-CT · Tumorbewegung

Tables 1. Patient characteristics.

Tabellen 1. Patientencharakteristika.

Patient Age Gender Localization Histological type TNM Stage Chemotherapy# (years)

1 51 Male Left central Carcinoma microcellulare T3 N2 Mx IIIa Yes 2 53 Male Right central Adenocarcinoma Tx Nx M1 IV No 3 74 Female Right S6 Adenocarcinoma T2 N0 M1 IV Yes 4 59 Male Left upper lobe Carcinoma planocellulare T3 N2 M0 IIIa No 5 61 Male Left upper lobe Carcinoma planocellulare T2 N2 M0 IIIa No 6 43 Male Right lower lobe central Carcinoma planocellulare T2 N2 M0 IIIa Yes 7 53 Male Left central Carcinoma microcellulare T4 N1 M1 IVb Yes 8 72 Male Right upper lobe Carcinoma planocellulare T2 N0 M0 II No 9 71 Male Left upper lobe Carcinoma planocellulare T3 N1 M0 III No 9 71 Male Left upper lobe Carcinoma planocellulare T3 N1 M0 III No 10 69 Female Right central Carcinoma microcellulare T2 N0 M1 IVb Yes

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hands on a hand holder. The patient position was also controlled in the x-y-z-axes, using lasers. Four radiopaque markers were temporally sticked on the chest wall: • the first marker in the longitudinal cen-

ter body axis, at the level of the second intercostal space,

• the second marker also in the longitu-dinal center body axis, two finger-breadths distant from the xiphoid pro-cess cranially,

• the third and fourth markers at the level of the second marker, on the left and right side, in the outer axillary line (Figure 2).

After placement of the markers, a tailored ORFIT® thermoplastic tho-racic mask was prepared for each pa-tient. The masks were melt at 78 °C, then tailed on to the patient’s body and precisely fixed to avoid any displace-ment within the mask. It was essential that the mask should perfectly follow the body contour without any free spaces between the patient’s body and the mask. Laser signs corresponding to all three axes were marked for the po-sitioning.

The training of breathing exercises was performed in the therapy simulator (Siemens® Simeview Simulator). After an acclimation period of 5 min, all patients had to breathe in normal amplitude, with a breath holding of 30 s follow-ing maximal inhalation, and then holding the breath expired at maximal exhalation. Only those patients were assigned to participate in the study who were able to breathe quietly and to hold their breath 30 s at maximal inhalation and 15 s at maximal exhalation.

CT Imaging After preparation, the patients were examined in the mul-tislice CT unit (SIEMENS® Somatom Sensation 16 Cardiac CT device). The patient immobilization system was placed on the flat treatment couch and the patients were localized in the original position, set in the simulator. The accuracy of posi-tioning was controlled by lasers in all three axes. Topometric CT scanning was performed, then the measurements were made with the same settings (continuous slice thickness of 8 mm with 2-mm interspaces, same starting points and end-points, range of same length), without marker and patient dis-placement. In addition to the routine procedure, four further measurements were performed for each patient: • with mask at normal breathing, • at maximal tidal volume inhalation,

• at maximal tidal volume exhalation, • then, the same measurements were repeated in unchanged

position, without mask. With the use of fast scan CT, the duration of one measure-

ment was < 20 s and the total examination time did not exceed 3 min.

From CT data acquired, 2-mm slices were depicted and reconstructed axially, coronally and sagittally; then, three di-mensional reconstructions were made.

Measurements were performed by E-RAD Practice Builder and PACS® Software eRAD/ImageMedical. At stan-dardized windowing (L = 440 HU, W = 45 HU), picture series were paired and the following parameters were analyzed (Fig-ure 3): (1) Analysis of chest wall motions: – upper marker displacement (as compared to the table

board), – lower medial marker displacement (as compared to the

table board), – lower lateral marker displacement (distance between the

markers). (2) Analysis of diaphragmatic movements: – Deviations of both diaphragms (distance between the in-

tersection of clavicle and second rib and the cranial pole of diaphragm in millimeters).

Figure 1. Thermoplastic patient immobilization system combined with hand holder.

Abbildung 1. Thermoplastisches Patientenimmobilisierungssystem mit kombiniertem Hand-halter.

Figure 2. Placement of the markers on the patient’s body.

Abbildung 2. Lage der Marker auf dem Körper des Patienten.

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(3) Analysis of tumor motions (the measurements were per-formed starting from the point of intersection of the great-est tumor diameters reconstructed in three planes):

– distance between the tumor center and the longitudinal center body axis,

– distance between the tumor center and the lateral chest wall,

– distance between the tumor center and the anterior chest wall,

– distance between the tumor center and the posterior chest wall,

– craniocaudal displacement of the tumor center.

Statistical Analysis For data evaluation, the paired t-test was used. When compar-ing the data series, the mean values were confronted in all cases and, during evaluation, a significance level of p ≤ 0.05 was considered to be a significant difference.

Results Movements of chest wall (Figure 4), diaphragm (Figure 5) and tumor (Figure 6), with and without mask fixation, were registered. When comparing the data acquired, the average of maximal deviation was taken into account. As maximal devia-tion, the difference of maximal inhalation and maximal exha-lation was evaluated.

Upper Marker Displacement Mean maximal displacement of upper marker, with and with-out mask, was 10.5–7.7 mm (p ≤ 0.05). Concerning the upper markers, the difference was found to be significant with the use of the immobilizing system.

Lower Medial Marker Displacement Mean maximal displacement of lower medial marker, with and without mask, was 10–7.4 mm (p ≤ 0.05). For the lower medial markers, a significant difference was ob-served.

Lower Lateral Displacement Mean maximal transverse displacement of markers in the lower outer axillary line, with and without mask, was 8.1–4.2 mm (p ≤ 0.05). A significant difference was observed in this case as well.

Figure 3. Measurement of tumor movements and chest wall.

Abbildung 3. Messung der Tumorbewegung und der Brustwand.

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Figure 4. Marker motions. Left columns represent motions without, and right columns motions with the mask fixation system. Column 11 shows the mean values.

Abbildung 4. Markerbewegungen. Die linken Säulen repräsentieren Bewegungen ohne, die rechten Säulen Bewegungen mit Maskenfixie-rungssystem. Säule 11 zeigt die Durchschnittswerte.

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Diaphragmatic Movements Mean maximal displacement of the right diaphragm, with and without mask, was 41.7–40.5 mm (p ≤ 0.5), and of the left diaphragm 40.5–36.8 mm (p ≤ 0.1). Concerning diaphragmatic movement, no significant difference was observed.

Tumor Motions Median displacement of tumor motions, with and without mask, was 15.3–12.4 mm in craniocaudal direction (p ≤ 0.2), 11.5–8.8 mm in posteroanterior direction (p ≤ 0.15), 4.6–4.1 mm in medial direction (p ≤ 0.5), and 7.2–5 mm in lateral direc-

Figure 6. Tumor motions. Left columns represent motions without, and right columns motions with the mask fixation system. Column 11 shows the mean values.

Abbildung 6. Tumorbewegungen. Die linken Säulen repräsentieren Bewegungen ohne, die rechten Säulen Bewegungen mit Maskenfixie-rungssystem. Säule 11 zeigt die Durchschnittswerte.

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Figure 5. Diaphragm motions. Left columns represent motions without, and right columns motions with the mask fixation system. Column 11 shows the mean values.

Abbildung 5. Zwerchfellbewegungen. Die linken Säulen repräsentieren Bewegungen ohne, die rechten Säulen Bewegungen mit Maskenfixie-rungssystem. Säule 11 zeigt die Durchschnittswerte.

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tion (p ≤ 0.1). A significant difference was not observed. In case of anteroposterior tumor motions (mean: 8.9–6.3 mm), a significant difference was registered at a significance level of p ≤ 0.05.

Discussion With the rapid technological development and the use of three-dimensional irradiation in recent years, an increased interest in monitoring of internal organ motions during radio-therapy can be observed. This question is of great importance in the radiotherapy of lung tumors, because in this localiza-tion a considerable range of organ and tumor motions is to be expected [2, 8, 14]. Since deviations arising from tumor mo-tions have to be taken into account, the size of PTV must be increased significantly. However, due to the side effects, the radiation dose is limited by the volume of the normal tissues. If uncertainties resulting from tumor motions will not be con-sidered when performing PTV delineation, this involves the risk that the CTV cannot be covered as required, and conse-quently, the delivery of an adequate tumor-destroying dose becomes doubtful [2, 4, 8].

Our purposes with this study were to detect, describe and analyze tumor motions and to assess the effectiveness of our immobilization system regarding tumor motion restriction.

To reduce the uncertainties coming from tumor motions, Kutcher et al. presented four options [22]: • monitoring of tumor motions and consideration of the re-

sults thereof at outlining of a definitive therapeutic plan, • patient training: breath control technique, • delivering of a triggered, breathing-synchronized irradia-

tion, • active blocking of patient’s respiration.

Up to now, several authors discussed the monitoring of tumor motions. At the beginning, the respiratory cycle was ex-amined by fluoroscopic measures; however, these techniques include some disadvantages. There is the possibility of an over- or underestimation of the actual movement, if the tumor is not located at a defined distance from the focus because of magnifying and lessening effects, and sometimes (central or small tumors) the exact definition of the tumor may be diffi-cult [31, 35]. Other authors applied beam imaging systems for monitoring tumor motions. A major advantage of this proce-dure is the real-time imaging, but portal imaging did not be-come very popular; in addition, visualization qualities need to be improved anyway [26, 27].

CT-based definition of the tumor motion is the most pop-ular and simplest method. According to this most commonly used procedure, the definition of PTV is performed on the ba-sis of CT images taken under normal breathing conditions. In general, the anatomic position seen on the image taken in nor-mal breathing is considered to be a mid-position between in- and exhalation. However, the examination results clearly showed that the position of diverse thoracic structures during normal breathing can by no means be regarded as interposi-

tion between in- and exhalation [3, 13, 34]. Incorrect anatomic definition shall lead to geometric inaccuracy [3]. This pre-sumption is confirmed by our present results as well. Due to our results the breathing-synchronized motions of the chest wall and the tumor are of a considerable extent, even with mask fixation.

With the development of imaging technology, a new al-ternative in monitoring of organ motions is the use of dy-namic MRI. Currently, only a few data are available, but the early results are promising, suggesting that MRI can be a powerful future device to improve the efficiency of the mon-itoring of tumor motions and of irradiation planning [16, 28, 30, 33]. The other promising method is four-dimensional CT. The four-dimensional CT image acquisition system combines the physiological displacements induced by several respira-tory phases, representing the images of the diverse phases [15, 29].

During this study, we had to eliminate two critical prob-lems. The first was the question of patient immobilization as-sociated with the reduction of tumor motions, the second the selection of reference points used.

Up to now in the literature, several authors described their investigations relating to respiratory-gated techniques and active blocking of patient respiration, and movements. The question of immobilization is a principal issue of modern radiotherapy. It is helpful in eliminating the inaccuracies aris-ing from positioning errors as well as in reducing treatment time setting and in most precisely reproducing the status at planning. The application of immobilization became more popular from the 1960s and 1970s. By now, several forms of positioning systems (mask fixation, vacuum systems, arm holders, etc.) are known [36]. Breathing-synchronized, manu-ally triggered linac treatments are also in use, during which therapy is controlled by respiratory positions transmitted by video equipment or a plethysmograph [20, 21]. Some authors reported on treatments in deep breath hold with active control allowing a CTV reduction of 0.25 cm, resulting in a decrease of the dosage-induced damage to normal lung tissues [12, 32]. Several papers were published relating to employment of ac-tive breath control (ABC) technique [24, 39]. Major disadvan-tages of the above techniques are their complexity and great demand on resources.

According to our own experience, the rigid system used at our institute is an easily and relatively fast feasible device. It is well tolerable for patients and, furthermore, patient po-sitioning does not take much time. Our results clearly show that this device reduces displacements of the bony chest wall considerably. It has to be noted that the application of mask fixation did not produce a significant effect on the tumor mo-tions; moreover, in some cases increased tumor motions could be observed during the use of the mask (Figure 6). Of course, this fact depends greatly on tumor localization, so a future examination in this regard is of outstanding impor-tance.

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Selection of the comparison points was a critical question. During respiration almost all parts of the chest are moving, it is difficult to find fixed points of reference. In their study, DeNeve et al. defined diaphragm, chest wall, carina and inter-vertebral disk as bases of comparison [7]. This method was followed also by Giraud et al. [11]. Besides diaphragm and chest wall, we used the anatomic medial line defined by the vertebrae, as well as radiopaque markers, put on fixed, prop-erly reproducible anatomic points to perform the measure-ments. Our results represent comparative values, since – dis-regarding the vertebrae – all points of reference are in breathing-synchronized motion.

Conclusion The great advantages of the immobilization system used by our team include its simple construction, uncomplicated opera-tion and, according to our experience, its relatively high ef-fectiveness in positioning of lung cancer patients. Our meas-urements show that, besides the advantage of optimal patient positioning, the movements of the bony chest wall can be con-siderably reduced by using this system. During use of this mask fixation system, we noted a decrease in tumor motions as well, but not at a significant level. This system is not able to reduce breath-related tumor motions.

Our results refer to the fact that the planning CT exami-nation applied in daily routine work cannot give exact details about the actual tumor position, because it takes a snapshot of the tumor location in a single moment; therefore, wide mar-gins are to be taken in account when defining the PTV.

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Address for Correspondence Prof. Dr. Akos Horvath Head of the Department of Radiotherapy Medical and Health Science Center University of Debrecen Nagyerdei Krt. 98. 4012 Debrecen Hungary Phone and Fax (+36/52) 453-585 e-mail: horvakos@freemail.hu