Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours

Abstract

Purpose: To quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark.

Methods: Seven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour.

Results: The average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively.

Conclusions: A significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.

Figure 1

Beams eye view of the posterior portal used in the IFP technique. This portal is composed by three segments: the first was conformal to the total PTV, whereas the second and third segments irradiated the PTV lying on the right and left side of the spinal cord, respectively. In this patient, the PTV1 includes the primary tumour and an adenopathy shown in brown. The high risk lymph nodes, PTV2, are shown in red and the low risk lymph nodes are shown in orange.

Figure 2

Average response values for P₊, P_B and P_I. Average values and standard deviation for the probability of uncomplicated tumour control, P₊, the total probability of tumour control, P_B, and the total probability of severe complications, P_I. Sophisticated radiation treatment techniques have significantly increased the probability of total tumour control first due to the prescribed dose escalation and second due to the biological dose escalation obtained with IMRT2. The probability of complications was already significantly reduced with IFP compared with CONVT, but with IMRT a further significant decrease was obtained. The differences obtained for the treatment outcome and the probability of complications between IMRT1 and IMRT2 were not statistically significant.

Figure 3

Probability of response and dosimetric data for several organs at risk. Average values of the probability of complications in each organ at risk, P_I, the mean dose, D_mean and the maximum significant dose, D_max. The error bars indicate the standard deviation of all planned cases. The colour bars show the biologically converted dose to a fractionation schedule of 2 Gy per fraction. The grey bars show nominal or physical dose values obtained with the prescribed fractionation. The larynx was not used during treatment planning in the past and therefore it was not included in treatment planning optimization. However with the prescribed dose escalation and to maximize normal tissue sparing all organs located close to the PTV should be delineated and considered during optimization.

Figure 4

Probability of tumour control and dosimetric data for the target volumes. Average values of the probability of tumour control in each target volume, P_B, the minimum significant dose, D_min, the mean dose, D_mean, the maximum significant dose, D_max, and the dose distribution standard deviation, SD. For illustration purposes this standard deviation was multiplied by 10. The error bars refer to the standard deviation of all planned cases. The colour bars indicate the dose values converted to a fractionation scheme of 2 Gy per fraction. The grey bars show the physical dose for the prescribed fractionation. The difference between the physical dose and converted dose to 2 Gy is more evident in the PTV1 due to repopulation effects.

Figure 5

Mean dose and probability of complications for the parotids. Mean dose, D_mean (above) and probability of complications, P_I (below) in the ipsilateral and contralateral parotid for each of the seven studied cases. Horizontal colour lines show average values for all patients. The dashed lines in the upper plots indicate the dose objective of 26 Gy generally used as the tolerance dose level in the parotids [25]. Dose values refer to biologically corrected dose to a fractionation of 2 Gy per fraction. Nasop. stands for nasopharynx, Orop. for oropharynx, Hipop. for hipopharynx and Tong. for base of the tongue.