Radiotherapy Treatment of Early-Stage Prostate Cancer with IMRT and Protons: A Treatment Planning Comparison
2007; Elsevier BV; Volume: 69; Issue: 2 Linguagem: Inglês
10.1016/j.ijrobp.2007.03.018
ISSN1879-355X
AutoresAlexei V. Trofimov, Paul L. Nguyen, John J. Coen, Karen P. Doppke, Robert J. Schneider, Judith Adams, Thomas Bortfeld, Anthony L. Zietman, Thomas F. DeLaney, William U. Shipley,
Tópico(s)Prostate Cancer Diagnosis and Treatment
ResumoPurpose: To compare intensity-modulated photon radiotherapy (IMRT) with three-dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT).Methods and Materials: Ten patients were planned with both 3D-CPT (two parallel-opposed lateral fields) and IMRT (seven equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the prostate gland. Dose–volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning.Results: At least 98% of the planning target volume received the prescription dose. IMRT plans yielded better dose conformity to the target, whereas proton plans achieved higher dose homogeneity and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more than 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, whereas rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was reduced by up to 35% compared with the standard lateral configuration, whereas the bladder V70 increased by less than 10%.Conclusions: In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range lower than 50% of the target prescription was substantially lower with proton therapy. Purpose: To compare intensity-modulated photon radiotherapy (IMRT) with three-dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT). Methods and Materials: Ten patients were planned with both 3D-CPT (two parallel-opposed lateral fields) and IMRT (seven equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the prostate gland. Dose–volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning. Results: At least 98% of the planning target volume received the prescription dose. IMRT plans yielded better dose conformity to the target, whereas proton plans achieved higher dose homogeneity and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more than 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, whereas rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was reduced by up to 35% compared with the standard lateral configuration, whereas the bladder V70 increased by less than 10%. Conclusions: In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range lower than 50% of the target prescription was substantially lower with proton therapy. IntroductionConformal proton therapy was first delivered to prostate cancer patients in 1976 at the Harvard Cyclotron, with the clinical support from Massachusetts General Hospital (MGH). Because the proton dose is largely deposited in the Bragg peak at the end of the particle’s range, with no dose delivered beyond a few millimeters past the peak, protons offer a great tool for sparing of the healthy tissue around the target. The method employed at the MGH Francis H. Burr Proton Therapy Center is three-dimensional conformal proton therapy (3D-CPT) using broad passively scattered proton beam (1Bussiere M.R. Adams J.A. Treatment planning for conformal proton radiation therapy.Technol Cancer Res Treat. 2003; 2: 389-399PubMed Google Scholar). Patient-specific devices are used to shape the radiation field: brass apertures for lateral and Lucite compensators for distal conformation. Uniform target coverage in depth is achieved by modulating the energy of the proton beam entering the patient’s body to create a spread-out Bragg peak.Since the first publication in 1979, based on 17 cases treated at MGH (2Shipley W.U. Tepper J.E. Prout Jr., G.R. et al.Proton radiation as boost therapy for localized prostatic carcinoma.JAMA. 1979; 241: 1912-1915Crossref PubMed Scopus (124) Google Scholar), clinical experience with protons in prostate cancer has grown greatly. In 1995, MGH reported on a phase III randomized trial of high-dose irradiation boosting with conformal protons to a dose of 75.6 cobalt Gray-equivalent (CGE), compared with conventional irradiation to 67.2 Gy using photons alone for patients with stage T3-T4 disease (3Shipley W.U. Verhey L.J. Munzenrider J.E. et al.Advanced prostate cancer: The results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.Int J Radiat Oncol Biol Phys. 1995; 32: 3-12Abstract Full Text PDF PubMed Scopus (363) Google Scholar). Loma Linda Proton Treatment Center published their initial experience with 1,277 patients with early disease, treated to 74 CGE, and found comparable disease-free survival with minimal morbidity, compared with other forms of local therapy (4Slater J.D. Rossi Jr., C.J. Yonemoto L.T. et al.Proton therapy for prostate cancer: The initial Loma Linda University experience.Int J Radiat Oncol Biol Phys. 2004; 59: 348-352Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar). Recently, a randomized two-arm dose-escalation trial that involved a mix of photons and protons to treat localized prostate cancer at MGH and Loma Linda, found that irradiation to 79.2 vs. 70.2 CGE produced a significantly superior 5-year prostate-specific antigen failure-free survival (5Zietman A.L. DeSilvio M.L. Slater J.D. et al.Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: A randomized controlled trial.JAMA. 2005; 294: 1233-1239Crossref PubMed Scopus (1051) Google Scholar).Because protons are still a rather limited resource, it is important to identify the sites in which proton therapy offers appreciable advantage over the more readily available conformal treatments, such as intensity-modulated radiotherapy (IMRT) with photons.Patients with early prostate cancer were among the first to benefit from the clinical use of IMRT in the mid-1990s (6Burman C. Chui C.S. Kutcher G. et al.Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: A strategy for large-scale implementation for the treatment of carcinoma of the prostate.Int J Radiat Oncol Biol Phys. 1997; 39: 863-873Abstract Full Text PDF PubMed Scopus (254) Google Scholar). By employing advanced inverse treatment planning techniques, IMRT allowed for improvement in the dose distribution conformity to the tumor volume, and, consequently, a reduction in irradiation of the healthy surrounding tissue. Although the dosimetric advantage of IMRT over the standard 3D-CPT has been widely reported (7De Meerleer G.O. Vakaet L.A. De Gersem W.R. et al.Radiotherapy of prostate cancer with or without intensity modulated beams: A planning comparison.Int J Radiat Oncol Biol Phys. 2000; 47: 639-648Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar, 8Ma L. Yu C.X. Earl M. et al.Optimized intensity-modulated arc therapy for prostate cancer treatment.Int J Cancer. 2001; 96: 379-384Crossref PubMed Scopus (41) Google Scholar, 9Zhu S. Mizowaki T. Nagata Y. et al.Comparison of three radiotherapy treatment planning protocols of definitive external-beam radiation for localized prostate cancer.Int J Clin Oncol. 2005; 10: 398-404Crossref PubMed Scopus (30) Google Scholar, 10Zelefsky M.J. Fuks Z. Wolfe T. et al.Locally advanced prostatic cancer: Long-term toxicity outcome after three-dimensional conformal radiation therapy–a dose-escalation study.Radiology. 1998; 209: 169-174PubMed Google Scholar, 11Teh B.S. Mai W.Y. Uhl B.M. et al.Intensity-modulated radiation therapy (IMRT) for prostate cancer with the use of a rectal balloon for prostate immobilization: Acute toxicity and dose-volume analysis.Int J Radiat Oncol Biol Phys. 2001; 49: 705-712Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar), a comprehensive planning comparison of IMRT and proton radiation therapy has not been performed thus far.Cella et al. compared 3D-conformal and intensity-modulated proton and photon plans for a single case of prostate cancer (12Cella L. Lomax A. Miralbell R. Potential role of intensity modulated proton beams in prostate cancer radiotherapy.Int J Radiat Oncol Biol Phys. 2001; 49: 217-223Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar); Mock et al. compared 3D-CPT and proton plans with photon IMRT for 5 patients (13Mock U. Bogner J. Georg D. et al.Comparative treatment planning on localized prostate carcinoma conformal photon- versus proton-based radiotherapy.Strahlenther Onkol. 2005; 181: 448-455Crossref PubMed Scopus (65) Google Scholar). However, the proton range uncertainty was not taken into account in the design of treatment plans.The primary purpose of this study was to determine the relative dosimetric benefits and disadvantages of IMRT vs. 3D-CPT for patients with prostate cancer, taking into account proton range uncertainty. Second, we investigated the utility, for prostate cancer, of intensity-modulated proton therapy (IMPT).Similar to IMRT with photons, IMPT delivers individually inhomogeneous dose distributions from various directions to yield the desired distribution. IMPT can be delivered by magnetically scanning a narrow proton beam across the target volume. Beam intensity and speed are varied during the scan to achieve the desired dose modulation, and the beam energy is adjusted for irradiation of specific layers of equal radiologic depth within the target. In this way, IMPT makes it possible to conform the dose to the proximal edge of the target, in addition to the distal edge (as in 3D-CPT). Unlike 3D-CPT, IMPT does not require patient-specific range compensators. Consequently, IMPT avoids the additional proton beam scattering in the compensator material, upstream from the patient, and reduces the degradation of the dose penumbra in tissue. IMPT treatments have not yet been delivered in the United States. Work on the implementation of clinical IMPT is currently under way at MGH.The experience with IMPT at the Paul Scherrer Institut (Switzerland) demonstrated a potential for improved tissue sparing in a number of sites, including intracranial, nasopharyngeal and paraspinal lesions (14Lomax A.J. Boehringer T. Coray A. et al.Intensity modulated proton therapy: A clinical example.Med Phys. 2001; 28: 317-324Crossref PubMed Scopus (208) Google Scholar, 15Lomax A.J. Pedroni E. Rutz H. et al.The clinical potential of intensity modulated proton therapy.Z Med Phys. 2004; 14: 147-152Crossref PubMed Scopus (130) Google Scholar, 16Weber D.C. Lomax A.J. Rutz H.P. et al.Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas.Radiother Oncol. 2004; 71: 251-258Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 17Weber D.C. Trofimov A.V. Delaney T.F. et al.A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas.Int J Radiat Oncol Biol Phys. 2004; 58: 1596-1606Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 18Weber D.C. Rutz H.P. Pedroni E.S. et al.Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: The Paul Scherrer Institut experience.Int J Radiat Oncol Biol Phys. 2005; 63: 401-409Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar). Although intensity modulation has been identified as a means to achieve prostate dose escalation (12Cella L. Lomax A. Miralbell R. Potential role of intensity modulated proton beams in prostate cancer radiotherapy.Int J Radiat Oncol Biol Phys. 2001; 49: 217-223Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar), IMPT treatment of prostate cancer has not yet been performed anywhere.Methods and MaterialsPatient selectionAfter approval by the MGH investigational review board for this treatment planning comparison study, we randomly selected 10 patients with clinically localized early-stage prostate cancer, who were treated with protons. Among patients who require radiation treatment to the prostate and seminal vesicles only (i.e., not the pelvic nodes), the choice between IMRT and proton therapy at MGH is most commonly based on the treatment slot availability and patient preferences, rather than any clinical characteristics.Treatment simulationComputed tomography scanning was performed in the supine position with the resolution between 0.93 and 0.98 mm in the axial planes, and the slice thickness of 2.5 mm. The attending physician outlined the entire prostate, the most caudal 1-cm section of the seminal vesicles, the entire rectal wall from the junction with the sigmoid colon to the anus, urinary bladder, penile bulb, and femoral heads.For each patient, the gross tumor volume (GTV) was considered the prostate gland, and the clinical target volume (CTV) was defined as the whole prostate and caudal seminal vesicles. Two planning volumes, planning target volume (PTV)1 and PTV2 were defined as 5-mm uniform expansions around CTV and GTV, respectively. Dose prescriptions were applied as recommended in Radiation Therapy Oncology Group (RTOG) protocol 0126 (Table 1). The CTV prescription dose was 50.4 Gy or CGE (for protons), and the GTV prescription was 79.2 Gy/CGE. For conversion to CGE, the physical dose was multiplied by the radiobiologic effectiveness of the proton, which was assumed to be 1.1 relative to Co-60.Table 1Treatment plan objectivesTarget prescription doses GTV (prostate)100% to 79.2 Gy/CGE CTV (GTV and seminal vesicles)100% to 50.4 Gy/CGE PTV2 (GTV + 5-mm margin)98% to 79.2 Gy/CGE PTV1 (CTV + 5-mm margin)98% to 50.4 Gy/CGETolerance doses for healthy organs Rectum<50% to 60 Gy/CGE<35% to 65 Gy/CGE<25% to 70 Gy/CGE<15% to 75 Gy/CGEMaximum 84.7 Gy/CGE Bladder<50% to 65 Gy/CGE<35% to 70 Gy/CGE<25% to 75 Gy/CGE<15% to 80 Gy/CGEMaximum 84.7 Gy/CGE Femoral headMaximum 50 Gy/CGE Penile bulbMean dose < 52.5 Gy/CGEAbbreviations: GTV = gross tumor volume; CGE = cobalt Gray-equivalent; CTV = clinical target volume; PTV = planning target volume. Open table in a new tab The average GTV volume was 67 mL (30 mL minimum, 120 mL maximum, 56 mL median). The sizes of target volumes for all patients are given in Table 2.Table 2Size of target volumes, total volume of tissue irradiated to prescription doses, and conformity indices for PTV1CaseTarget volume (mL)Volume irradiated to 79.2 Gy/CGE (mL)Volume irradiated to 50.4 Gy/CGE (mL)PTV1 conformity indexGTVPTV2PTV1IMRT3D-CPTIMRT3D-CPTIMRT3D-CPT1541041451381853744422.583.0521161942232403485626862.523.083306896961302783222.903.35449991221131793634002.983.2851202052492643606817212.732.906551071501381734033982.692.657851561792062465125402.863.028561121421361923654432.573.129561131381381813784472.743.231049961141161693173872.783.39Mean671251561592164234792.733.11Abbreviations: CGE = cobalt Gray-equivalent; GTV = gross tumor volume; PTV = planning target volume; IMRT = intensity-modulated radiotherapy; 3D-CPT = 3D-conformal proton therapy. Open table in a new tab Treatment planningClinical 3D-CPT plans were created with CMS/XiO software (CMS Inc., St. Louis, MO). Two equally weighted parallel-opposed lateral fields were used to deliver the prescribed dose to the CTV and the boost dose to the GTV. The dose was calculated on a 2 × 2 × 2.5 mm3 grid.Although the sharp dose falloff beyond the proton Bragg peak presents a valuable tool for tissue sparing, precise positioning of the distal dose gradient is complicated by the uncertainties in the proton penetration depth. In a fractionated treatment course, radiologic path length for the incoming proton beam may vary day to day because of misalignment of tissue inhomogeneities, especially bony structures, and the compensator, as the result of variation in the patient positioning (19Urie M. Goitein M. Holley W.R. et al.Degradation of the Bragg peak due to inhomogeneities.Phys Med Biol. 1986; 31: 1-15Crossref PubMed Scopus (99) Google Scholar). To ensure adequate PTV coverage despite the uncertainties in alignment with bony structures that will be introduced by shifts made as part of the daily image-based patient setup, a technique called “compensator smearing” is employed at the MGH proton center. An idealized range compensator is first designed by the treatment planning system based on the planning computed tomography data. The compensator map consists of hexagonal elements of 3 mm in diameter (Fig. 1). Each element is assigned the thickness of material needed to stop the protons at the distal surface of the target volume. Typically, the 98% isodose is matched to the planning target outline (1Bussiere M.R. Adams J.A. Treatment planning for conformal proton radiation therapy.Technol Cancer Res Treat. 2003; 2: 389-399PubMed Google Scholar). The “smear” algorithm is then applied, in which each of the hexagonal elements is reassigned the thickness to the value that is the lowest among its nearest neighbors within the given “smear radius.” This procedure ensures that misalignments within the smear radius will not compromise the dose coverage of the PTV. However, consequently, the prescription isodose surface is pushed beyond the PTV surface and, inevitably, the dose to healthy tissue distally to the target is increased. Prostate treatment plans typically employ the smear radius of 10 mm.A clinical physicist used Corvus treatment planning software (NOMOS Corp., Sewickley, PA) to create the photon IMRT plans. All plans employed seven coplanar beams of 6 MV, spaced by 50° from the posterior direction. The plans were optimized for delivery with a multileaf collimator of 5×5 mm2 resolution at the isocenter.Because, beyond a narrow buildup region close to the skin surface, the photon dose falls off exponentially with depth, the consequence of errors associated with tissue inhomogeneities is typically not as grave as in the case of the protons. However, the interfractional motion of prostate, bones of the hip, and other changes related to rectal or bladder filling may significantly affect the conformity of treatment (20Bos L.J. van der Geer J. van Herk M. et al.The sensitivity of dose distributions for organ motion and set-up uncertainties in prostate IMRT.Radiother Oncol. 2005; 76: 18-26Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). In the presence of position uncertainties, PTV margins ensure the target coverage with IMRT.To explore the potential for treatment improvement, several experimental proton plans were optimized for selected patients. These included 3D-CPT plans in which dose was delivered from anterior-oblique direction, and IMPT plans optimized for delivery with proton pencil beam scanning.Unlike the clinical plans that used parallel-opposed lateral beams (gantry angles of 90° and 270°), experimental 3D-CPT plans were optimized with the beams rotated toward the anterior direction (e.g., for a 20° anterior rotation, to 70° and 290°). This allowed for taking advantage of the sharp distal penumbra of the proton beam. At the typical depth of target in prostate treatments (20–30 cm water-equivalent), the lateral penumbra of the proton beam deteriorates substantially because of Coulomb scattering and becomes roughly twice as wide as the distal penumbra. However, in the current clinical practice, the use of distal gradients for dose conformation is avoided because of the uncertainty in the proton penetration depth.Treatment plans for IMPT were created with KonRad Pro software, developed at German Cancer Research Center. KonRad employs inverse planning methods to optimize relative weights of individual pencil beams to achieve the desired dose coverage (21Oelfke U. Bortfeld T. Inverse planning for photon and proton beams.Med Dosim. 2001; 26: 113-124Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 22Trofimov A. Bortfeld T. Optimization of beam parameters and treatment planning for intensity modulated proton therapy.Technol Cancer Res Treat. 2003; 2: 437-444PubMed Google Scholar, 23Nill S. Bortfeld T. Oelfke U. Inverse planning of intensity modulated proton therapy.Z Med Phys. 2004; 14: 35-40PubMed Google Scholar). IMPT plans used lateral parallel-opposed beam configuration, and were optimized for delivery with a pencil beam of σ = 5 mm (approximately 12-mm full width at half-maximum, as projected for the MGH proton scanning nozzle).Planning margins, identical to those in respective IMRT plans, were used to ensure the target coverage with IMPT. Because IMPT dose is modulated in three dimensions (laterally and in depth), dose homogeneity may be affected by misestimating the proton radiation depth. To ensure the dose uniformity and its conformity to the target, real-time monitoring of IMPT delivery may be needed (e.g., using positron emission tomography) (24Parodi K. Ponisch F. Enghardt W. Experimental study on the feasibility of in-beam PET for accurate monitoring of proton therapy.IEEE Trans Nucl Sci. 2005; 52: 778-786Crossref Scopus (102) Google Scholar, 25Parodi K. Bortfeld T. A filtering approach based on Gaussian-powerlaw convolutions for local PET verification of proton radiotherapy.Phys Med Biol. 2006; 51: 1991-2009Crossref PubMed Scopus (80) Google Scholar).Treatment deliveryAt MGH, prostate patients are treated in supine position. Immobilization is achieved with commercially available rigid devices, such as the leg abductor (Alimed Inc., Dedham, MA). Daily pretreatment imaging with a B-mode Acquisition and Targeting ultrasound probe (NOMOS Corp.) is used to align the target with the treatment field, for both IMRT and 3D-CPT. Except for hip rotation, setup is identical for IMRT and proton therapy.Application of smear algorithm in the proton compensator design ensures that the effect of the setup uncertainties on the radiologic path length to the target does not compromise the target dose coverage. Portal X-ray imaging is performed daily during the first week of treatment to ensure correct positioning of the range compensator with respect to the bony anatomy and the prostate (26Engelsman M. Rosenthal S.J. Michaud S.L. et al.Intra- and interfractional patient motion for a variety of immobilization devices.Med Phys. 2005; 32: 3468-3474Crossref PubMed Scopus (48) Google Scholar). If the alignment of bony anatomy from portal imaging and prostate from ultrasound is consistently within the 5-mm agreement, X-ray imaging is performed weekly for the rest of the course (whereas target localization and alignment using the ultrasound probe are still done daily for all patients). In fewer than 5% of prostate treatment courses, in which the default smear radius of 10 mm is judged as insufficient, a new compensator is manufactured with increased smear.All 10 subjects of this study were treated with 3D-CPT. Two lateral fields were used to deliver the prescription dose to the CTV in 25 fractions, followed by the 16-fraction dose boost to the GTV.End pointsDose–volume histograms (DVH) were calculated for all volumes of interest. The DVH parameters used in the comparison of IMRT and proton plans included the minimum, mean, maximum doses, for targets; D35% (i.e., the dose exceeded in 35% of the given volume), D25%, D15%, and D2% for healthy organs. Also compared were the fractional volumes that received a certain dose (e.g., V60 [the fraction of the volume of interest that received at least 60 Gy/CGE], V70). The Wilcoxon matched-pair signed-rank test was applied to evaluate the level of significance of the observed difference between dose–volume metrics. The threshold of statistical significance was set at p ≤ 0.05.Equivalent uniform doses (EUD) were evaluated as EUD =[1N∑iN(di)α]1/α, where α is a tissue-specific parameter, and N is the total number of points (voxels), and i is the volume of interest for which the physical dose di was calculated (27Niemierko A. Reporting and analyzing dose distributions: A concept of Equivalent Uniform Dose (EUD).Med Phys. 1997; 24: 17-26Crossref PubMed Scopus (23) Google Scholar, 28Niemierko A. A generalized concept of equivalent uniform dose.Med Phys. 1999; 26 ([abstract]): 1100Google Scholar). The parameter α is typically positive for healthy organs and negative for target volumes. The values of α were kindly provided by A. Niemierko, Ph.D. (MGH). The EUD for target volumes were calculated with α = −10−5+3, where the subscript and superscript designate the uncertainty margins (95% confidence). EUD were evaluated for the central (most probable) value of α, as well as the uncertainty bounds: for example, for a target, α = −10 (central value), −15 (lower bound), and −7 (upper bound). The values of a for healthy organs were as follows: α = 7−3+5 for the bladder, α = 5−2+3 for the rectum.The dose conformity index was calculated as the ratio of the prescription isodose volume to the volume of the corresponding target. If target coverage is equivalent for two plans, the one with better dose conformity will have a smaller conformity index. Ideally, conformity index would be one, if the prescription isodose coincides with the target surface.ResultsDose delivery to targetPlan objectives with respect to the target coverage were fulfilled in all cases: at least 98% of PTV2 received 79.2 Gy/CGE. Minimum, mean, and maximum GTV and CTV doses are given in Table 3.Figure 2 shows 3D-CPT and IMRT dose distributions in the transversal isocenter plane for Patient 1. The corresponding DVHs are plotted in Fig. 3. For Patient 2, sample dose distributions and corresponding DVHs are shown, respectively, in Fig. 4, Fig. 5.Table 3Minimum, mean, and maximum doses planned for target volumesTarget volumeDose metricIMRT plans (Gy)3D-CPT plans (CGE)Average of 10 plansRange (min–max)Average of 10 plansRange (min–max)GTVD-min79.979.2–82.379.579.2–80.3D-mean83.581.7–86.181.180.4–82.4D-max87.784.3– 90.083.282.0–85.4CTVD-min69.462.0–74.960.852.2–75.2D-mean83.081.0–84.580.477.6– 81.8D-max87.784.3–90.083.282.0–85.4Abbreviations: CGE = cobalt Gray-equivalent; GTV = gross tumor volume; CTV = clinical target volume; IMRT = intensity-modulated radiotherapy; 3D-CPT = 3D-conformal proton therapy; D-min = minimum dose; D-mean = mean dose; D-max = maximum dose. Open table in a new tab Fig. 2Patient 1: dose distribution in the transversal isocenter section from (a) intensity-modulated radiation therapy, (b) three-dimensional conformal proton therapy, and (c) intensity-modulated proton therapy plans. Dashed white lines show the contours of the prostate, planning target volume (PTV1), rectum, bladder, and femoral heads.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 3Patient 1: dose–volume histograms from intensity-modulated radiation therapy, three-dimensional conformal proton therapy (parallel-opposed lateral beam configuration, labeled “lat”), and intensity-modulated proton therapy plans.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 4Patient 2: dose distributions from (a) intensity-modulated radiation therapy, (b) three-dimensional conformal proton therapy (3D-CPT) plan using parallel-opposed lateral beam configuration; the difference between doses delivered by these two plans is shown in (c). Dose distribution from the 3D-CPT plan using lateral-anterior-oblique beam configuration, with the beams rotated by 20° toward the anterior, is shown in (d). The outlines of the prostate, planning target volume (PTV1), rectum and femoral heads are designated as dashed white lines in (a, b, d), and solid green lines in (c).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 5Patient 2: dose–volume histograms (DVH) from intensity-modulated radiation therapy and three-dimensional conformal proton therapy plans with lateral parallel-opposed (“lat”), and anterior-oblique configurations with the beams rotated by 20° (“ao20”) and 50° (“ao50”) toward the anterior. DVH are shown for the gross tumor volume, bladder, right femoral head, whole rectum, and anterior and posterior rectal walls.View Large Image Figure ViewerDownload Hi-res image Download (PPT)IMRT dose distributions proved more conformal to the target, with the volume of the 79.2-Gy isodose reduced, on average, by 26% (p = 0.002), compared with 3D-CPT plans (Table 2). F
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