Massachusetts General Hospital is one of only a few sites worldwide that operate both IMRT and particle therapy facilities. Therefore, this study was able to draw on the unique first-hand experience in clinical treatment planning and therapy of prostate cancer. Previously, Cella et al.
reported on the comparison of 3D-conformal and intensity-modulated proton and photon plans for a single case (12
). The plans were designed with rather relaxed target coverage, with the prescription dose of 81 Gy delivered to roughly 50% of the PTV. Intensity-modulation (with either photons or protons, using the same 5-field configuration) improved target dose homogeneity, reduced normal tissue irradiation in the low and medium range (≤70% of the target dose), and allowed for escalation of the median target dose from 81 to 99 Gy. More recently, Mock et al.
compared treatment plans for 3D-CPT and photon IMRT for 5 patients, using the prescription dose of 70 Gy (13
). The difference in the rectum and bladder volumes that received 70% of the prescription dose was found to be insignificant, while the mean doses to healthy organs were reduced by between 40% and 80% with protons.
The plans presented in this manuscript used the target volume definitions and dose prescriptions recommended by RTOG protocol 0126. The 3D-conformal proton therapy plans were optimized for actual treatment courses delivered at MGH, and used standard strategies to minimize the effect of the delivery uncertainties. The reduction, with 3D-CPT vs. IMRT, of the mean dose to rectum (by 26%, on average) and bladder (by 20%) was not as significant as previously reported (12
). While IMRT achieved significant improvement in bladder sparing (e.g., V60
), neither appeared to have a clear advantage in rectal sparing in the high-dose range (over 70% of the GTV prescription).
In radiation treatment of prostate cancer, there is no single accepted predictive factor based on the dose to healthy tissue, which is correlated with treatment complications. Various clinical indications for the development of late rectal toxicity have been reported: e.g., irradiation of 40% of the whole rectal volume to 65 Gy (29
), 25% to 66 Gy (30
), 57% to 60 Gy (31
), or D25%
of 70 Gy (32
). Based on the data from randomized trials at MGH, Benk et al
. advised caution in raising more than 40% of the anterior rectal wall (or, roughly, 20% of the whole rectum) to 75 CGE (33
), while Hartford et al
. linked increased risk of rectal toxicity to irradiation of over 70% of the anterior wall to 60 Gy, and over 30% to 75 Gy (34
Among the cases examined in this study, Patient 5, who received 70 CGE to 26.5%, and 75 CGE to 21.3% of the whole rectal volume, according to the clinical 3D-CPT plan, indeed suffered from acute rectal toxicity. Incidentally, in the respective IMRT plan, only 16.6% of the rectal volume received 70 Gy or more, a reduction of almost 40% from the proton plan. For the same patient, V75 was smaller by nearly a factor of 2 with IMRT (11.0% vs. 21.3% with protons). In the other nine cases, for either 3D-CPT or IMRT, rectal V70 and V75 were all safely below the abovementioned risk-indicating levels. This result indicates that, due to their capacity for creating sharp dose gradients, intensity-modulated treatments (with photons or protons) are likely to decrease the odds of acute complications in prostate cancer patients in certain problematic anatomical configurations. In less challenging circumstances, the potential of intensity-modulation may not necessarily be engaged in full to achieve acceptable levels of organ sparing. Consequently, IMRT may be more suitable in cases where such complications appear likely, e.g. judging by the DVH metrics of 3D-conformal plans.
While, in terms of EUD, or in the physical dose range of 50 to 70 Gy, there appeared to be no significant difference in sparing of healthy tissue with either protons or IMRT, the protons irradiated substantially smaller volumes in the range up to 30 Gy. As more than 70% of all prostate cancers in the U.S. are diagnosed in males over age 65, the benefit of the integral dose reduction with protons may not be as appreciable as in younger age groups. However, recent reports of the increased risk of secondary malignancies in the older population, following prostate cancer radiotherapy (35
), indicate that the dose reduction may be practical in that demographic group as well.
Concerns have been raised about the effect of the whole-body dose from neutrons produced in proton interactions with, e.g., the beam-shaping devices during 3D-CPT treatments (38
). Notably, the compact (often referred to as “spherical”) shape of the target in prostate treatments allows for design of apertures, which are more material-efficient compared to those needed for targets having more complicated shapes. Thus, the amount of material in the beam path and, consequently, the dose from secondary particles are reduced. In the case of prostate treatment, roughly equal numbers of secondary neutrons are produced in proton interactions with the aperture material (externally), and the patient tissue (internally). Intensity-modulated proton therapy with a scanned pencil beam, IMPT may completely avoid the use of field-shaping apertures, and further reduce the dose from secondary particles.
IMPT is routinely delivered to cancer patients at PSI (Switzerland) (14
). The work on development and clinical implementation of IMPT is currently under way at MGH and other proton centers in the US and internationally. While beam scanning may initially be a more time-consuming and costly alternative to the established passive-scattering proton therapy, the differential is expected to abate as IMPT becomes a more common treatment option.
The uncertainty in the particle penetration depth is the main factor that limits sparing of healthy tissue with proton therapy. Currently, standard proton treatments of prostate cancer employ parallel-opposed lateral beams, which are considered least affected by the proton range uncertainty. However, lateral approach is also associated with the largest radiological depth of the target, thus, higher scatter and wider dose penumbra. With improved range verification, proton dose conformity would improve substantially, especially with the possibility, offered by IMPT, to conform to the target proximally. The improved dose conformity to the target, in turn, will make feasible the target dose escalation while maintaining adequate sparing of healthy organs.