Biologically Effective Dose-Volume Analysis for Patients Treated with Moderately Hypofractionated IMRT for Unresectable Lung Cancer

Abstract

Routine use of intensity modulated radiation therapy (IMRT) for patients with unresectable lung cancer remains controversial, especially if done with hypofractionated approach. Moreover, published dose-volume limits for risk organs have been based on pooled-analyses of historical data without concern for biological consequence due to spatial variation of dose per fraction. Such can be exacerbated by using IMRT, but may be mitigated per concept of biologically effective dose (BED). We hypothesize that BED-based dosimetry can help clinicians quantify risk-benefit ratios for IMRT versus traditional 3D-conformal radiotherapy (CRT) and identify the better treatment strategy accordingly. Ten patients with unresectable lung cancer near esophagus received IMRT using moderately hypofractionated regimens (median dose per fraction 2.4 Gy, range: 2.25 to 2.5 Gy; median total dose 62.5 Gy, range: 60 to 63 Gy). Dosimetric outcomes were compared between 3D-CRT via shrinking-field technique and IMRT using volumetric modulated arc therapy (VMAT) via simultaneously integrated boost (SIB) technique. Physical doses were converted into BED and linear-quadratic equivalent dose based on 2-Gy per fraction (LQED2). The respective a/b values for tumor control, late- and acute-side effects were set at 10, 3 and 9 Gy. Dose-volume histograms (DVH) were generated using BED or LQED2. The average tumoricidal LQED2 for this VMAT-treated cohort was 63.7±1.5 Gy (BED: 76.4±1.8 Gy10), while the corresponding figure for 3D-CRT was 61.6±1.6 Gy (BED: 73.9±1.9 Gy10). For acute esophagitis, the respective average percent volumes receiving minimal LQED2 of 35 (V35) and 50 (V50) Gy (BED: 42.8 and 61.1 Gy9) for 3D-CRT were 41.4±12.4% and 34.8±13.1%, while the corresponding figures for VMAT were 33.1±13.4% and 16.2±13.9%. For late esophagitis, the respective average V35 and V50 (BED: 58.3 and 83.3 Gy3) for 3D-CRT were 40.4±12.3% and 31.8±14.6%, while the corresponding figures for VMAT were 31.7±13.4% and 14.3±13.7%. Similarly, for late pulmonary toxicity, the respective average V20 and V45 (BED: 33.3 and 75 Gy3) for 3D-CRT were 31.2±8.7% and 11.2±3.6%, while the corresponding figures for VMAT were 21.5±7.3% and 6.1±4.0%. Thus, while VMAT delivered higher tumoricidal dose, it actually predicted lower toxicities than 3D-CRT. IMRT via VMAT seems to have therapeutic advantage over 3D-CRT per radiobiological consideration. This study demonstrates the utilization of BED- or LQED2-based dosimetry in order to provide clinicians quantitative comparisons amongst various treatment techniques. The “double-trouble” arising from altered fractionation schemes could be ameliorated. With the increasing popularity of IMRT and hypofractionated regimens, DVH guidelines based on BED or LQED2 might be useful but still subject to further clinical verification.