Dosimetric evaluation of the feasibility of stereotactic body radiotherapy for primary lung cancer with lobe-specific selective elective nodal irradiation

摘要

The present study was approved by the Institutional Review Board of our hospital (No. 13R-091). The patients included in this study had clinically diagnosed Stage I primary lung cancer, as defined by the Union International Contre le Cancer (UICC). Between January 2010 and June 2012, 24 patients were treated with SBRT for Stage I primary lung cancer in our institution. Of these patients, three were excluded from the study because they were treated with a reduced radiation dose that was different from that of our protocol (one patient; 6.5 Gy × 7 fractions, two patients; 6 Gy × 10 fractions) due to a violation in the dose constraints of SBRT for at-risk organs. Data from 21 patients were available for this study. The patient characteristics are shown in Table id="xref-table-wrap-1-1" class="xref-table" href="#T1">1. The patients were fixed in the supine position on a body support immobilization system (Engineering System, Nagano, Japan) with the upper extremities raised using a vacuum pillow for the dorsal aspect of the thorax and a thermoplastic shell for the ventral aspect of the thorax. Tumor movement was fluoroscopically measured prior to treatment planning. An abdominal compression device, equipped with a body support system to reduce respiratory motion, was used when the tumor moved more than 1 cm due to respiration. Serial CT images for treatment planning were acquired with 2-mm slice thickness in the target area and 5-mm in the remaining area, using a 4-row multi-detector CT scanner (HiSpeed NX/I GE Medical Systems, Milwaukee, WI), from the neck to the upper abdomen. The gross tumor volume (GTV) was delineated as the visible tumor at the lung window setting (window width 800 Hounsfield units (HU) and window level –600 HU), using a 3D radiation treatment planning system (Eclipse, Varian Associates, Palo Alto, CA). Two-phase CT images, which consisted of an inspiratory breath-holding phase and an expiratory breath-holding phase, were obtained to determine the range of tumor movement, and a long-scan-time CT with an 8-s scan time in free breathing was also obtained to determine the trajectory of tumor movement. GTVs were contoured on each of the three images to generate the internal GTV from their fusion. The clinical target volume (CTV) for SBRT (CTVsrt) was defined as the internal GTV plus an additional 5–8 mm margin, and the planning target volume (PTV) for SBRT (PTVsrt) was created by a 3-mm expansion of the CTVsrt in all directions. The dose was prescribed at the center of the PTV, and the PTV was covered with an isodose line between 80 and 90% of the prescription dose. The leaf margins were adjusted in an effort to improve conformity. The radiation doses were calculated using an analytical anisotropic algorithm (AAA) implemented in Eclipse 10.0.28 with heterogeneity correction. The calculation grid size was 0.25 × 0.25 × 0.25 cm. All patients were treated using 6-MV X-rays with non-coplanar static fields (ranging from 7 to 9 fields). Radiation treatment was then performed after image verification with 2D matching of the kilovoltage planar image and 3D matching of cone-beam CT acquired with the Varian on-board imaging (OBI) system equipped at the linear accelerator (CLINAC 21EX, Varian Medical Systems, Palo Alto, CA). The dose constraints of our protocol were determined based on the Japan Clinical Oncology Group (JCOG) Phase II clinical trial for Stage IA NSCLC (JCOG 0403 protocol) in consideration of other reports [id="xref-ref-12-1" class="xref-bibr" href="#ref-12">12–id="xref-ref-14-1" class="xref-bibr" href="#ref-14">14]. Table id="xref-table-wrap-2-1" class="xref-table" href="#T2">2 shows the dose constraints used at our institution. Protocol 1 was of the utmost priority. When treatment planning could not fulfill the Protocol 1 dose constraint of SBRT, then Protocol 2 was adopted. If the recalculated plan could not fulfill Protocol 2, then the patient was judged ineligible for SBRT. A search using the PubMed electronic database was conducted using the words ‘non–small cell lung cancer', ‘lymph node metastasis' and ‘Stage I' to determine the optimal selective ENI fields. The criteria by which we selected articles were: a sufficient number of cases, pathological findings, and reference to the frequency and location of lymph node metastasis according to primary sites. We found 10 articles that met the above criteria and provided useful information for our study. A summary of these articles is as follows. To evaluate the total biological dose of the two treatment plans comprising SBRT and the additional ENI plan, we used biologically equivalent doses of 2 Gy per fraction (EQD2) from the linear quadratic (LQ) formula with an α/β of 3 for late-responding tissues (i.e. the lung, esophagus and tracheobronchial wall) and an α/β of 2 for the spinal cord using the following equation for the SBRT plan: class="disp-formula" id="disp-formula-1"> class="mathjax mml-math