title: Inverse and forward optimization of one- and two-dimensional intensity-modulated radiation therapy-based treatment of concave-shaped planning target volumes: the case of prostate cancer.
abstract: BACKGROUND
  Intensity-modulated radiation therapy (IMRT) was suggested as a suitable technique to protect the rectal wall, while maintaining a satisfactory planning target volume (PTV) irradiation in the case of high-dose radiotherapy of prostate cancer. However, up to now, few investigations tried to estimate the expected benefit with respect to conventional three-dimensional (3D) conformal radiotherapy (CRT).
  
  
  OBJECTIVE
  Estimating the expected clinical gain coming from both 1D and 2D IMRT against 3DCRT, in the case of prostate cancer by mean of radiobiological models. In order to enhance the impact of IMRT, the case of concave-shaped PTV including prostate and seminal vesicles (P+SV) was considered.
  
  
  METHODS
  Five patients with concave-shaped PTV including P+SV were selected. Two different sets of constraints were applied during planning: in the first one a quite large inhomogeneity of the dose distribution within the PTV was accepted (set (a)); in the other set (set (b)) a greater homogeneity was required. Tumor control probability (TCP) and normal tissue control probability (NTCP) indices were calculated through the Webb-Nahum and the Lyman-Kutcher models, respectively. Considering a dose interval from 64.8 to 100.8 Gy, the value giving a 5% NTCP for the rectum was found (D(NTCP(rectum)=5%)) using two different methods, and the corresponding TCP(NTCP(rectum)=5%) and NTCP(NTCP(rectum)=5%) for the other critical structures were derived. With the first method, the inverse optimization of the plans was performed just at a fixed 75.6 Gy ICRU dose; with the second method (applied to 2/5 patients) inverse treatment plannings were re-optimized at many dose levels (from 64.8 to 108 Gy with 3.6 Gy intervals). In this case, three different values of alpha/beta (10, 3, 1.5)were used for TCP calculation. The 3DCRT plan consisted of a 3-fields technique; in the IMRT plans, five equi-spaced beams were applied. The Helios Inverse Planning software from Varian was used for both the 2D IMRT and the 1D IMRT inverse optimization, the last one being performed fixing only one available pair of leaves for modulation. A previously proposed forward 1D IMRT 'class solution' technique was also considered, keeping the same irradiation geometry of the inversely optimized IMRT techniques.
  
  
  RESULTS
  With the first method, the average gains in TCP(NTCP(rectum)=5%) of the 2D IMRT technique, with respect 3DCRT, were 10.3 and 7.8%, depending on the choice of the DVHs constraints during the inverse optimization procedure (set (a) and set (b), respectively). The average gain (DeltaTCP(NTCP(rectum)=5%)) coming from the inverse 1D IMRT optimization was 5.0%, when fixing the set (b) DVHs constraints. Concerning the forward 1D IMRT optimization, the average gain in TCP(NTCP(rectum)=5%) was 4.5%. The gain was found to be correlated with the degree of overlapping between rectum and PTV. When comparing 2D IMRT and 1D IMRT, in the case of the more realistic set (b) constraints, DeltaTCP(NTCP(rectum)=5%) was always less than 3%, excepting one patient with a very large overlap region. Basing our choice on this result, the second method was applied to this patient and one of the remaining. Through the inverse re-optimization of the treatment plans at each dose level, the gain in TCP(NTCP(rectum)=5%) of the inverse 2D technique was significantly higher than the ones obtained by applying the first method (concerning the two patients: +6.1% and +2.4%), while no significant benefit was found for inverse 1D. The impact of changing the alpha/beta ratio was less evident in the patient with the lower gain in TCP(NTCP(rectum)=5%).
  
  
  CONCLUSIONS
  The expected benefit due to IMRT with respect to 3DCRT seems to be relevant when the overlap between PTV and rectum is high. Moreover, the difference between the inverse 2D and the simpler inverse or forward 1D IMRT techniques resulted in being relatively modest, with the exception of one patient, having a very large overlap between rectum and PTV. Optimizing the inverse planning at each dose level to find TCP(NTCP(rectum)=5%)e level to find TCP(NTCP(rectum)=5%) can improve the performances of inverse 2D IMRT, against a significant increase of the time for planning. These results suggest the importance of selecting the patients that could have significant benefit from the application of IMRT.
authors.affiliation: Servizio di Fisica Sanitaria, H San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Corletto
authors.forename: Mauro
authors.initials: M
authors.lastname: Iori
authors.forename: Marta
authors.initials: M
authors.lastname: Paiusco
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Brait
authors.forename: Sara
authors.initials: S
authors.lastname: Broggi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ceresoli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Iotti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calandrino
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000379:methods*; D011882:Radiotherapy, High-Energy; D016896:Treatment Outcome