Dose distribution and tumor control probability in out-of-field lymph node stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy (3D-CRT) of non-small-cell lung cancer: an in silico analysis

The advent of IMRT and image-guided radiotherapy (IGRT) in combination with involved-field radiotherapy (IF-RT) in inoperable non-small-cell lung cancer results in a decreased incidental dose deposition in elective nodal stations. While incidental nodal irradiation is considered a relevant by-product of 3D-CRT to control microscopic disease this planning study analyzed the impact of IMRT on dosimetric parameters and tumor control probabilities (TCP) in elective nodal stations in direct comparison with 3D-CRT. The retrospective planning study was performed on 41 patients with NSCLC (stages II-III). The CTV was defined as the primary tumor (GTV + 3 mm) and all FDG-PET-positive lymph node stations. As to the PTV (CTV + 7 mm), both an IMRT plan and a 3D-CRT plan were established. Plans were escalated until the pre-defined dose-constraints of normal tissues (spinal cord, lung, esophagus and heart) were reached. Additionally, IMRT plans were normalized to the total dose of the corresponding 3D-CRT. For two groups of out-of-field mediastinal node stations (all lymph node stations not included in the CTV (LN_all-el) and those directly adjacent to the CTV (LN_adj-el)) the equivalent uniform dose (EUD) and the TCP (for microscopic disease a D50 of 36.5 Gy was assumed) for the treatment with IMRT vs 3D-CRT were calculated. In comparison, a significantly higher total dose for the PTV could be achieved with the IMRT planning as opposed to conventional 3D-CRT planning (74.3 Gy vs 70.1 Gy; p = 0.03). In identical total reference doses, the EUD of LN_adj-el is significantly lower with IMRT than with 3D-CRT (40.4 Gy vs. 44.2 Gy. P = 0.05) and a significant reduction of TCP with IMRT vs 3D-CRT was demonstrated for LN_all-el and LN_adj-el (12.6 % vs. 14.8 %; and 23.6 % vs 27.3 %, respectively). In comparison with 3D-CRT, IMRT comes along with a decreased EUD in out-of-field lymph node stations. This translates into a statistically significant decrease in TCP-values. Yet, the combination of IF-RT and IMRT leads to a significantly better sparing of normal tissues and higher total doses whereas the potential therapeutic drawback of decreased incidental irradiation of elective lymph nodes is moderate