An evaluation of two techniques for beam intensity modulation in patients irradiated for stage III non-small cell lung cancer
Introduction
The local tumor control in locally advanced non-small cell lung cancer (NSCLC) is poor after radiotherapy (RT) alone and a pathological complete response was only seen in 20% of patients who were treated to 65 Gy [1]. Improvements in local control in this group of patients can improve survival [2], [3]. In locally advanced NSCLC, treatment with induction chemotherapy (CHT) followed by RT is superior to RT alone [1], [4], [5]. A recent study also suggested that the concurrent administration of CHT and RT is superior to sequential treatment [6]. However, concurrent CHT and RT can significantly increase the incidence of early and late radiation-induced grade 3/4 toxicities [7]. Data from patients treated using 3-dimensional (3D) conformal radiotherapy (CRT) suggest that a dose of 84 Gy may be required in order to achieve a likelihood of local control in excess of 50% [8]. However, efforts to escalate RT doses have been limited by toxicity [9] and/or have resulted in considerable dose inhomogeneity in the tumor [4].
The volume of healthy lung tissue receiving a dose exceeding 20 Gy (V20) has been shown to predict for radiation pneumonitis [10]. Similarly, the length of esophagus in the RT field has been shown to correlate with esophagitis [11], [12]. Consequently, steps to decrease the volume of irradiated normal tissue and/or improvements in radiation dose-homogeneity may reduce the toxicity of combined treatments. One approach to reduce normal tissue toxicity would be by not irradiating the radiologically normal mediastinum, i.e. ‘involved-field’ RT. In an ongoing phase II clinical trial at our center, patients with inoperable stage III NSCLC are treated with induction chemotherapy, followed by ‘involved-field’ RT to a dose of 70 Gy. This trial tests the hypothesis that isolated recurrences in the radiologically normal mediastinum are likely to be uncommon after ‘involved-field’ RT, thereby permitting radiation dose-escalation and/or CHT-RT with acceptable normal tissue toxicity. To achieve the latter, we are exploring alternative planning techniques, which can further increase normal tissue sparing.
Dose distributions delivered by multiple-field irradiation techniques can often be significantly improved by modulating the 2D intensity profile of the individual X-ray beams. Such intensity modulated beam (BIM) profiles can be realised in many ways including static multileaf collimation [13], dynamic multileaf collimation [14], [15] and tissue compensators [16]. Accurate missing tissue compensators can be made using a set of closely spaced CT scans to construct the 3D anatomy and to obtain density information for making tissue inhomogeneity corrections [17]. Such 3D tissue compensators have been shown to improve dose homogeneity in patients with tumors of the head and neck [18] and breast [19]. This technique is used at our institute in the treatment of patients with head and neck cancer [20].
In this planning study, our current 3D conformal radiation technique (CRT) for lung cancer patients was compared with 2 BIM techniques, namely: (a) BIM using missing tissue compensators (C-BIM), and (b) a technique using static BIM with a multileaf collimator to sharpen the penumbra at the superior and inferior ends of the planning target volume (PTV), thereby allowing a reduction in the penumbra margin between the field edge and the PTV [21], (BF-BIM). The resulting plans were compared using ICRU 50 homogeneity criteria, dose volume histograms (DVH's), mean lung dose [22], and percentage of the total lung volume exceeding 20 Gy (V20) [10]. The latter two parameters are often used to predict the risk of radiation pneumonitis.
Section snippets
Material and methods
In our phase II trial, patients with inoperable stage III tumors are treated with either two or four cycles (the latter when at least a partial response has been observed) of carboplatin and paclitaxel, followed by RT to a dose of 70 Gy, in once-daily fractions of 2 Gy, to the gross tumor volume (GTV), i.e. tumor and mediastinal nodes with a short-axis diameter ≥1 cm (Table 1). Patients with supraclavicular lymphadenopathy, malignant pleural effusions or tumors exceeding 6 cm were ineligible
Results
The ten patients had tumors located in the upper lobe or hilar regions, and details of the primary tumor, nodal metastases and PTV's are summarized in Table 1. The mean PTV of the ten patients was 407.4±144.7 cc (1 S.D.). Four of the ten patients had a partial response after the initial two cycles of CHT, but one patient in this cohort was unable to receive the fourth cycle of CHT due to an episode of (unrelated) cholecystitis. Six out of ten patients were judged to have stable disease but one
Discussion
Despite the omission of RT to the uninvolved mediastinum, 3/10 patients treated with conventional CRT to 70 Gy experienced acute radiation pneumonitis requiring treatment with glucocorticoids. Although concurrent CHT-RT with paclitaxel has been reported to result in an increase in the incidence of radiation pneumonitis [27], this has not been reported when RT follows the completion of paclitaxel-containing schemes. In any case, the high V20 values (Table 3) seen with CRT planning for our
Conclusions
Despite thoracic RT using an ‘involved-field’ approach in patients with mainly stage 3B inoperable NSCLC, acceptable V20 values (≤35%) were not achieved in the majority of patients. By enabling a consistent reduction in the V20, BIM techniques appear to be a promising tool in studies evaluating RT dose-escalation and/or intensive concurrent CHT-RT.
Acknowledgements
The assistance of Dr E. van Dieren with the ‘Optimize’ program is gratefully acknowledged.
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