Rectal Equivalent Uniform Dose Research Articles

44. Metamodelling of late rectal bleeding in patients undergoing radiotherapy for prostate cancer

Purpose To develop a modelling procedure for late rectal bleeding (LRB) that goes beyond maximum likelihood model fitting of data. Thus, to create a metamodel for grade 2–3 (G23) and grade 3 (G3) LRB starting from literature evidence and validate it on a large population. Methods Metamodelling allows to highlight specific features of the model itself. Characteristics that predictive models for LRB have in common are: the global harmony of radiobiological parameters (volume effect parameter, n, steepness of the curve, k, and dose parameter associated to 50% of complication probability, D50) and specific clinical factors that frequently occur. Models including rectal Equivalent Uniform Dose (EUD) with/without patient-related dose-modifying factors (DMF) were retrieved by literature search. Dosimetric coefficients were resolved by weighted mean of published values, using their standard deviation as weight. Identified clinical features, expressed by DMF, were differently weighted taking into account the prevalence of the features and the size of the study. Finally, both factors were inserted in a modified logit-EUD model. Metamodel was validated on a pooled population (3DCRT/IMRT) of three international cohorts. Performance was assessed through calibration. Results Literature search identified rectal EUD, previous abdominal surgery, hormone therapy and use of cardiovascular drugs as relevant features: associated coefficients are presented in Table 1 . Validation cohort included 1591 pts with 240 (15%) LRBG23 and 98 (6.2%) LRBG3 pts. The calibration (Fig. 1) showed the following results: concerning LRBG23 the slope was equal to 0.22 (R2 = 0.38); the corresponding values for LRBG3 were 1.12 and 0.97. Conclusions A metamodel for prediction of LRB was derived from literature. LRBG3 model was successfully validated on a large population proving to be a valuable tool for predicting toxicity before RT. The model for LRBG23 predicted very well toxicity rate below 25% (which involved 87% of the population) while partially failing at higher probabilities.

Metamodeling of late rectal bleeding in patients undergoing radiotherapy for prostate cancer.

61 Background: Predictive models for late rectal bleeding (LRB) after radiotherapy (RT) for prostate cancer were established by several studies, with good performance on development population (POP). Nonetheless, they were found to be unsatisfactory in their generalization to independent validation cohorts. Aim of the study is to build a metamodel for grade 2-3 (G23) and grade 3 (G3) LRB (LENT/SOMA) starting from literature evidence and to validate it on a new POP. Methods: The metamodel was constituted by clinical/dosimetric features and by their coefficients. Available predictive models for LRB were selected by literature search. Models including rectal Equivalent Uniform Dose (EUD) with/without patient-related dose-modifying factors were retrieved. The process allowed identification of “evidence-based” clinical/dosimetric features associated to LRB. Coeff. for identified features were resolved by weighted mean of published values, using their standard deviation as weight and then inserted in a sigmoid-shaped logit-EUD model. The resulting metamodel was validated on a pooled POP of radically treated pts (3DCRT & IMRT). Performance was assessed through calibration. Results: The search identified rectal EUD, previous abdominal surgery (SURG), hormone therapy (HT) and use of cardiovascular drugs (CARDIO) as relevant features (coeff. presented in table). Validation POP included 1591 pts with 240 (15%) LRBG23 and 98 (6.2%) LRBG3 pts. Calibration was very good: LRBG23 slope = 1.4 with R2 = 0.86; LRBG3 slope = 1.1 with R2 = 0.96. Conclusions: A metamodel for prediction of LRB has been developed from literature, including all currently available information on association between LRB and clinical/dosimetric factors. The model was successfully validated on a large POP, proving to be a valuable tool for predicting LRB before RT. [Table: see text]

Dose-volume consistency and radiobiological characterization between prostate IMRT and VMAT plans

Purpose: Dose-volume consistency of the planning target volume (PTV) and rectum for the prostate intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were evaluated and compared. Dependences of radiobiological parameters of the prostate and rectum on the PTV and rectal volume were also investigated. Methods: From 40 prostate IMRT and 50 VMAT patients treated with the same prescription (78 Gy per 39 fractions) and dose-volume criteria in the inverse planning, the prostate tumour control probability (TCP), rectal equivalent uniform dose (EUD) and rectal normal tissue complication probability (NTCP) were calculated. The dose-volume consistency of the PTV and rectum, demonstrating the variability of dose-volume histogram (DVH) among patients, was defined and calculated as per the deviation between the corresponding and mean DVH. Results: For the IMRT plans, the prostate TCP was found increasing with the PTV with a rate equal to 1.05 × 10 -3 % cm -3 , which was lower than 1.11 × 10 -3 % cm -3 for the VMAT plans. Both the rectal EUD and rectal NTCP were found decreasing with the rectal volume. The decrease rates for the IMRT plans (EUD = 0.47 × 10 -3 Gy cm -3 and NTCP = 3.94 × 10 -2 % cm -3 ) were higher than those for the VMAT (EUD = 0.28 × 10 -3 Gy cm -3 and NTCP = 2.61 × 10 -2 % cm -3 ). Conclusion: For the dose-volume consistency, small prostate TCP variation could be achieved by decreasing the dose-volume variability among the IMRT and VMAT plans. However, dependences of the rectal EUD and rectal NTCP on the dose-volume variability were not significant. It is concluded that maintaining a good dose-volume consistency in prostate plans can decrease the prostate TCP variation among the IMRT and VMAT patients. However, dose-volume variability is not affected by variations of the rectal EUD and rectal NTCP.

SU-F-T-378: Evaluation of Dose-Volume Variability and Parameters Between Prostate IMRT and VMAT Plans

Purpose: This study compared the rectal dose-volume consistency, equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) in prostate intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: For forty prostate IMRT and fifty VMAT patients treated using the same dose prescription (78 Gy/39 fraction) and dose-volume criteria in inverse planning optimization, the rectal EUD and NTCP were calculated for each patient. The rectal dose-volume consistency, showing the variability of dose-volume histogram (DVH) among patients, was defined and calculated based on the deviation between the mean and corresponding rectal DVH. Results: From both the prostate IMRT and VMAT plans, the rectal EUD and NTCP were found decreasing with the rectal volume. The decrease rates for the IMRT plans (EUD = 0.47 × 10−3 Gy cm−3 and NTCP = 3.94 × 10−2 % cm−3) were higher than those for the VMAT (EUD = 0.28 × 10−3 Gy cm−3 and NTCP = 2.61 × 10−2 % cm−3). In addition, the dependences of the rectal EUD and NTCP on the dose-volume consistency were found very similar between the prostate IMRT and VMAT plans. This shows that both delivery techniques have similar variations of the rectal EUD and NTCP on the dose-volume consistency. Conclusion: Dependences of the dose-volume consistency on the rectal EUD and NTCP were compared between the prostate IMRT and VMAT plans. It is concluded that both rectal EUD and NTCP decreased with an increase of the rectal volume. The variation rates of the rectal EUD and NTCP on the rectal volume were higher for the IMRT plans than VMAT. However, variations of the rectal dose-volume consistency on the rectal EUD and NTCP were found not significant for both delivery techniques.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

SU-E-T-552: Maximizing the Biological Effect of Proton Dose Delivered with Scanned Beam.

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and controlled distribution of proton's linear energy transfer (LET). We evaluate potential gain in therapeutic effect from delivery of daily inhomogeneous fractional dose distributions in pencil beam scanning proton therapy (PBS-PT). For cases of prostate cancer, we considered a hypofractionated course of 20 fractions of 3 Gy (assuming α/β=1.5, the equivalent dose in 2-Gy fractions (ED2Gy) is 77.1 Gy). Two sets of dose distributions were planned using two opposed lateral fields to deliver a uniform dose: (1) in full-target plans (FTP) each beam targeted the entire gland (2) in split-target plans (STP), beams targeted only the respective proximal hemispheres (prostate split sagittally). Linear combinations of optimized beam intensity maps from FTP and STP, for a variety of mixing weights, were used to evaluate inhomogeneous fractional dose (IFD) distributions. IFD delivered doses boosting either hemisphere in alternating fractions, e.g., alternating between 40% and 160% of the nominal fractional dose (1.2-4.8 Gy). The equivalent uniform dose (EUD) was calculated for ED2Gy distributions. IFD plans were rescaled so that the EUD of rectum and bladder did not increase. LET distributions were calculated with Monte Carlo, and compared for different plans. In the IFD courses, the whole prostate received a nearly uniform dose in every 2 fractions, however EUD was higher than in conventional FTP by up to 8%. Rectal EUD decreased by 2%, and bladder EUD was unchanged. The LET distributions of FTP and STP were distinctly different, thus, in IFD, LET depended strongly on the mixing weights. In PBS-PT, modestly improved therapeutic outcome can be expected with delivery of inhomogeneous daily dose distributions, while administering the prescribed dose to target over the entire course. The biological effectiveness may be further enhanced by optimizing the LET distributions. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.

TH‐C‐BRA‐04: Endorectal Balloons in Post‐Prostatectomy: Do Gains in Stability Lead to More Predictable Dosimetry?

Purpose: To perform a comparative study assessing potential benefits of endorectal balloons (ERB) in post‐prostatectomy patients Methods: Ten retrospective post‐prostatectomy patients without ERB and ten prospective patients with the ERB in situ were treated with IMRT using kilo voltage cone beam computed tomography (kVCBCT) image guidance (IGRT). A kVCBCT dataset from each treatment week was registered to the planning dataset, recontoured and the original plan recalculated on the kvCBCTs to recreate actual anatomical conditions during treatment. The imaging, structure and dose data were imported into Matlab. In house applications analysed geometric variation in the two groups and calculated cumulative equivalent uniform dose (EUD). Results: Analysis of the kVCBCT datasets showed that the ERB improved target volume stabilization from millimetre to sub‐millimetre reproducibility. The variation in bladder location in the non ERB cohort was 1.5 ± 0.9 cm compared to 0.6 ± 0.4 in the ERB group. While the superior rectum location variation was 1.1 ± 0.8 cm and 0.3 ± 0.3 cm for non ERB and ERB respectively. The mean difference in cumulative EUD and planned EUD for the clinical target volume (CTV) was 0.6 ± 0.04 Gy for non ERB and 0.4 ±0.1 Gy for ERB. The largest normal tissue differences were seen for the bladder with an increase of 4.4 ± 0.1 Gy for non ERB and 1.2 ± 0.02 Gy for ERB in the cumulative compared with the planned EUD. Differences in delivered superior rectal EUD was improved in the ERB cohort with a difference of−0.2 ± 0.04 Gy verse 3.0 ± 0.3 Gy in the non ERB group. Conclusions: The ERB cohort was found to have more stable and reproducible anatomy when compared to the non ERB cohort. Planned and cumulative EUD differences were greatest for the bladder and rectum.

SU‐E‐T‐652: Rectal Equivalent Uniform Dose Analysis on the Prostate IMRT for Interfraction Organ Motion Using the Gaussian Error Function

Purpose: The aim of this study is to verify the calculation of rectal equivalent uniform dose (EUD) using the Gaussian error function (GEF), which can reduce the dose‐volume database to enhance the computing efficiency. Methods: For a group of 20 prostate patients, cumulative dose‐volume histograms (cDVHs) for the rectum, shifted in the anterior—posterior directions based on a 7‐beam IMRT plan, were calculated and modeled using the Pinnacle3 treatment planning system (TPS) and GEF, respectively. The range of rectal shift for each patient was measured by daily electronic portal imaging with fiducial gold markers in the prostate. The shape of cDVH curve was fitted into the GEF model, and then the cDVHs were converted to corresponding differential DVHs to calculate the rectal EUDs in each interfraction organ motion. Results: Rectal EUD was calculated per fraction to determine the equivalent dose at each movement step. Our results showed that rectal EUDs increased as the rectum shifted to anterior direction and decreased in the posterior direction. Moreover, it is found that rectal EUDs have a negative linear relationship with respect to the organ displacement. Based on the results, the patient with the smallest prostate (volume = 40 cc) in the group received the highest rectal EUD when the rectum shifted 8 mm anterior. Percentage difference of rectal EUD using the TPS and GEF has been calculated for each movement. Since the results are less than 0.5%, the GEF model is considered a good potential alternative of the TPS. Conclusions: We concluded that the calculation of rectal EUD using the GEF model was validated with error less than 0.5%.

SU‐E‐T‐659: Maximizing the Therapeutic Effect of a Fractionated Treatment with Delivery of Inhomogeneous Daily Dose Distributions

Purpose: To evaluate potential gain in therapeutic effect from delivery of daily inhomogeneous fractional dose distributions in proton therapy, using pencil beam scanning. Methods: For a sample case of prostate cancer, we consider a standard course of 39 fractions of 2 Gy (78 Gy total), and a hypofractionated course of 20 fractions of 3 Gy (assuming alpha/beta=1.5, the equivalent dose in 2 Gy fractions (ED2Gy) is 77.1 Gy). Two sets of dose distributions were planned: (1) the standard approach, with a uniform dose (100% of prescription) delivered in every fraction to the entire target; (2) delivery of inhomogeneous fractional dose (IFD) distributions, which varied within the target volume between 65% and 135% of the nominal prescription. For IFD, the daily distributions were optimized in such a way that the two hemispheres of the prostate (split sagittally through the urethra) received, in alternating fractions, either 65% or 135% of the nominal fractional dose (e.g., 1.3 and 2.7 Gy), while the urethra received approximately 100% (e.g., 2 Gy) daily. The equivalent uniform dose (EUD), and ED2Gy were compared for different plans. Results: In the IFD course, the whole prostate received a nearly uniform dose over every 2 fractions, however ED2Gy was higher than with standard uniform dose: 81.9 Gy (5% increase) for the conventional, and 82.6 Gy (7% increase) for the hypofractionated course. Rectal and bladder EUD increased by <5%, while urethral EUD was unchanged. Conclusions: In treatment of prostate and other sites, improved therapeutic outcome can be expected with delivery of inhomogeneous daily dose distributions, while administering the prescribed uniform dose to target over the entire course of treatment. The extent of expected gain is dependent on model parameters (alpha/beta, EUD‐a, etc.), and dose distributions may potentially be designed to maximize the gain specifically for a certain assumed range of parameters.No disclosures or conflict of interest. Supported by the Federal Share of program income earned on C06‐CA059267, Proton Therapy Research and Treatment Center.

Relationship Between Pelvic Organ-at-Risk Dose and Clinical Target Volume in Postprostatectomy Patients Receiving Intensity-Modulated Radiotherapy

To investigate dose-volume consequences of inclusion of the seminal vesicle (SV) bed in the clinical target volume (CTV) for the rectum and bladder using biological response indices in postprostatectomy patients receiving intensity-modulated radiotherapy (IMRT). We studied 10 consecutive patients who underwent prostatectomy for prostate cancer and subsequently received adjuvant or salvage RT to the prostate fossa. The CTV to planning target volume (PTV) expansion was 7 mm, except posterior expansion, which was 5 mm. Two IMRT plans were generated for each patient, including either the prostate fossa alone or the prostate fossa with the SV bed, but identical in all other aspects. Prescription dose was 68.4 Gy in 1.8-Gy fractions prescribed to ≥95% PTV. With inclusion of the SV bed in the treatment volume, PTV increased and correlated with PTV-bladder and PTV-rectum volume overlap (Spearman ρ 0.91 and 0.86, respectively; p < 0.05). As a result, the dose delivered to the bladder and rectum was higher (p < 0.05): mean bladder dose increased from 11.3 ± 3.5 Gy to 21.2 ± 6.6 Gy, whereas mean rectal dose increased from 25.8 ± 5.5 Gy to 32.3 ± 5.5 Gy. Bladder and rectal equivalent uniform dose correlated with mean bladder and rectal dose. Inclusion of the SV bed in the treatment volume increased rectal normal tissue complication probability from 2.4% to 4.8% (p < 0.01). Inclusion of the SV bed in the CTV in postprostatectomy patients receiving IMRT increases bladder and rectal dose, as well as rectal normal tissue complication probability. The magnitude of PTV-bladder and PTV-rectal volume overlap and subsequent bladder and rectum dose increase will be higher if larger PTV expansion margins are used.

Evaluation of the dosimetric impact of non-exclusion of the rectum from the boost PTV in IMRT treatment plans for prostate cancer patients

Purpose In dose escalation trial, for prostate cancer patients, zero CTV–PTV margins towards the rectum are often applied in the boost phase in order to avoid excessive dose delivery to the rectum. In this study, the dosimetric impact of non-exclusion of the rectum from the boost PTV is evaluated. Treatment plans created according to the protocol used in our institute for patients in a Dutch hypofractionated trial (HYPO), where the rectum is excluded from the boost PTV, were compared to plans designed with a modified version of this protocol (HYPO-exp) for which the rectal exclusion was not performed. Differences in target coverage and rectum dose were quantified. Methods and materials Treatment plans were generated for 36 prostate cancer patients. In the HYPO plans, the CTV–PTV margins around the prostate were 6 mm (7.5 mm at the caudal side) and 10 mm around the seminal vesicles (PTV1). For the boost phase, these margins were reduced to 5 mm, but no margin was taken at the overlap with the rectum (PTV2). The margin prescription for HYPO-exp was identical to that for HYPO, except that the zero CTV–PTV margin towards the rectum was omitted. For the HYPO and HYPO-exp plans, a simultaneous integrated boost technique using IMRT was applied to deliver 72.2 Gy to PTV1 and 78 Gy to PTV2. For all plans, the dose to the rectum was compared using V 50, V 60, V 70 , the equivalent uniform dose (EUD), considering α = 9 and 1, respectively, and normal tissue complication probabilities (NTCPs). In addition, the dose coverage of PTV1 and PTV2 and the minimum dose in those volumes were quantified. To assess the clinical impact of differences in dose delivery to the rectum, both IMRT plans were also compared to a plan (DESC) based on the treatment protocol applied in our institute in a former national dose escalation trial, which in the meantime has a median follow-up of six years. Results Compared to HYPO, V 70 and the rectal EUD calculated with α = 9 were slightly higher for HYPO-exp, but the differences were not statistically significant. V 50, V 60 and the rectal EUD calculated with α = 1 were similar for both the IMRT plans. In contrast, each of these parameters was significantly lower compared to DESC ( p < 0.001). The coverage of the boost PTV, used in HYPO-exp, by at least 95% of the prescribed dose was significantly better for HYPO-exp than for HYPO ( p < 0.001). In the overlap of this volume with the rectum, the minimum dose increased by 1.1 ± 1.2 Gy for HYPO-exp ( p = 0.002) and the mean dose by 1.2 ± 1.5 Gy ( p = 0.001). Conclusion By omitting the zero margin towards the rectum, underdosages in the target volume are reduced significantly, while a clinically relevant increase in rectum exposure is not observed.

SU‐GG‐T‐427: Dose Painting to Combat Tumor Hypoxia While Sparing Urethra in Prostate IMRT: A Biologically‐Based Adaptive Approach Accounting for Setup Uncertainties and Organ Motion

Purpose: To explore means of incorporating prostate motion and setup uncertainties into biologically‐based adaptive IMRT optimization for Volumetric Modulated Arc Therapy (VMAT). Method and Materials: IMRT planning objectives were set to produce a dose distribution, which, after accounting for setup uncertainties and prostate motion, meets the following requirements. 1) The CTV is covered with the desired dose; 2) Hypoxia volumes arbitrarily drawn inside CTV are boosted; 3) Desired urethra sparing is achieved. The objective function was based on equivalent uniform dose (EUD). Repositioning data from five prostate patients with implanted fiducial markers were used. Systematic and random uncertainties for each patient were incorporated into an in‐house treatment planning platform for VMAT. During the optimization, the dose matrix was shifted based on the systematic error, then convolved with a pre‐calculated Gaussian kernel to account for random errors. For each of these patients seven plans were generated using uncertainty data accumulated in 5 fraction increments. Results: The urethra EUD increased by &gt;5Gy when the dose distribution from the static plan was propagated to account for geometrical uncertainties. In contrast, if uncertainties were accounted for in planning, urethra EUD was reduced without compromising CTV coverage (EUD decreased &lt;1.5Gy). For four of five patients, the repositioning data from the first five fractions was sufficient to account for uncertainty in planning. In the proposed biologically‐based optimization inclusive of uncertainties, the PTV is not required. Appropriate dose coverage of the CTV is intrinsically produced by the optimization procedure. Because this coverage is typically tight and patient specific, improved normal tissue sparing was achieved. The rectal EUD was lowered by up to 23Gy compared to static plans that utilize the generic PTV concept. Conclusion: Our approach allows the inclusion of geometrical uncertainties into biologically‐based optimization of IMRT. Partial uncertainty data are sufficient to produce an optimal plan.

Robust treatment planning for intensity modulated radiotherapy of prostate cancer based on coverage probabilities

Background and purpose To evaluate an optimization approach where coverage probabilities are incorporated into the optimization of intensity modulated radiotherapy (IMRT) to overcome the problem of margin definition in the case of overlapping planning target volume and organs at risk. Patients and methods IMRT plans were generated for three optimization approaches: based on a planning CT plus margin (A), on prostate and rectum contours from five pre-treatment CT plus margin (B), and on coverage probabilities (C). For approach (C), the probability of organ occupation was computed for each voxel from five pre-treatment CTs and the population distribution of systematic setup error and it was used as local weight in the costfunctions. Monte Carlo simulations of treatment courses were used to compute the probability distribution of prostate and rectal wall equivalent uniform dose (EUD). Results Treatment simulations showed best and most robust results for prostate and rectal wall EUD within the population for (C). For (A) the rectal wall EUD was on average about 1.5 Gy greater than in (C), while the prostate EUD was lower than those from (C) for most of the patients for (B) (especially for those with great organ motion). Conclusions The incorporation of coverage probabilities as local weights allows for dose escalation as well as improved rectal sparing and results in a safer and more robust IMRT treatment.

Dosimetric advantages of IMRT simultaneous integrated boost for high-risk prostate cancer

A sequential two-phase process, initial and boost irradiation, is the common practice for the radiotherapy management of high-risk prostate cancer. In this work, we explore the feasibility of using intensity modulated radiation therapy (IMRT) simultaneous integrated boost (SIB), a single-phase process, to simultaneously deliver high dose to the prostate and lower dose to the pelvic nodes. In addition, we introduce the concept of voxel-equivalent dose for the comparison of treatment plans. The SIB is designed to deliver the same dose (e.g., 45 Gy, 25 x 1.8 Gy) as the conventional method to the pelvic nodes and to deliver higher doses to prostate in the same 25 fractions (i.e., hypofractionation). The equivalent uniform dose (EUD) was used to determine suitable SIB fractionations that deliver the biologically equivalent doses to prostate. For tumor, the EUD was estimated based on the linear quadratic (LQ) model. The most recent LQ parameters derived from clinical data for prostate cancer were used. The sensitivity of LQ parameters was evaluated. The EUD for normal tissue was computed based on the widely used Lyman model. To be able to consider biologic effectiveness spatially (e.g., voxel by voxel), we propose a new concept, termed the voxel-equivalent dose (VED). The calculation of VED was similar to that for EUD, except that it was done within a voxel. To demonstrate dosimetric feasibility and advantages of the proposed IMRT SIB, we have performed a retrospective planning study on selected patient cases using commercial IMRT and three-dimensional (3D) planning systems. Four treatment scenarios were considered: (1) the conventional 3D plan for initial whole-pelvic irradiation and subsequent conventional 3D boost plan for prostate gland, (2) the conventional 3D plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, (3) IMRT plan for initial whole-pelvic irradiation and subsequent IMRT boost plan for prostate, and (4) IMRT SIB. EUDs and VED-based dose-volume histograms for prostate, pelvic nodes, small bowel, rectum, bladder, and other tissue for all 4 scenarios were compared. A series of equivalent hypofractionation regimens suitable for the IMRT SIB were obtained for high-risk prostate cancer. For example, the conventional treatment regimen of 42 x 1.8 Gy (EUD = 75.4 Gy) would be equivalent to a SIB regimen of 25 x 2.54 Gy. From the comparison of 3D VED dose distributions and dose-volume histograms between the SIB and the conventional two-phase irradiation, we found that the SIB offers better or equivalent dose conformity to prostate and pelvic nodes and better sparing to the critical structures. For example, for the 4 treatment scenarios with a prostate EUD of 75.4 Gy, the corresponding rectal EUDs are 67.1 (3D + 3D), 65.6 Gy (3D + IMRT), 63.7 Gy (IMRT + IMRT), and 62.0 Gy (SIB). A new IMRT simultaneous integrated boost strategy that irradiates prostate via hypofractionation while irradiating pelvic nodes with the conventional fractionation is proposed for high-risk prostate cancer. Compared to the conventional two-phase treatment, the proposed SIB technique offers potential advantages, including better sparing of critical structures, more efficient delivery, shorter treatment duration, and better biologic effectiveness.

Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery

To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of bladder wall and rectal wall for conventional IMRT vs. online IG-IMRT were 70.1% vs. 47.3%, and 79.4% vs. 72.2%, respectively. On average, a target dose increase of 13% (SD = 9.7%) can be achieved with online IG-IMRT based on rectal wall EUDs and 53.3% (SD = 15.3%) based on bladder wall EUDs. However, the variation (SD = 9.7%) is fairly large among patients; 27% of patients had only minimal benefit (<5% of dose increment) from online IG-IMRT, and 32% had significant benefit (>15%-41% of dose increment). The ideal maximum dose increment achievable with online IG-IMRT is, on average, 13% with respect to the dose-limiting organ of rectum. However, there is a large interpatient variation, ranging <5%-41%. The results can be applied to calibrate other practical online image-guided techniques for prostate cancer radiotherapy, when intratreatment organ motion/deformation and machine delivery accuracy are considered.