Single Course IMRT Plan to Deliver 45 Gy to Seminal Vesicles and 81 Gy to Prostate in 45 Fractions

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1 Technology in Cancer Research and Treatment ISSN Volume 5, Number 5, October (2006) Adenine Press (2006) Single Course IMRT Plan to Deliver 45 Gy to Seminal Vesicles and 81 Gy to Prostate in 45 Fractions We treat prostate and seminal vesicles (SV) to 45 Gy in 25 fractions (course 1) and boost prostate to 81 Gy in 20 more fractions (course 2) with Intensity Modulated Radiation Therapy (IMRT). This two-course IMRT with 45 fractions delivered a non-uniform dose to SV and required two plans and two QA procedures. We used Linear Quadratic (LQ) model to develop a single course IMRT plan to treat SV to a uniform dose, which has the same biological effective dose (BED) as that of 45 Gy in 25 fractions and prostate to 81 Gy, in 45 fractions. Single course IMRT plans were compared with two-course IMRT plans, retrospectively for 14 patients. With two-course IMRT, prescription to prostate and SV was 45 Gy in 25 fractions and to prostate only was 36 Gy in 20 fractions, at 1.8 Gy/fraction. With 45-fraction single course IMRT plan, prescription to prostate was 81 Gy and to SV was 52 or 56 Gy for a α/β of 1 and 3, respectively. 52 Gy delivered in 45 fractions has the same BED of 72 Gy 3 as that of delivering 45 Gy in 25 fractions, and is called Matched Effective Dose (MED). LQ model was used to calculate the BED and MED to SV for α/β values of Comparison between two-course and single course IMRT plans was in terms of MUs, dose-max, and dose volume constraints (DVC). DVC were: 95% PTV to be covered by at least 95% of prescription dose; and 70, 50, and 30% of bladder and rectum should not receive more than 40, 60, and 70% of 81 Gy. SV Volumes ranged from cc. With two-course IMRT plans, mean dose to SV was nonuniform and varied between patients by 48% (54 to 80 Gy). With single-course IMRT plan, mean dose to SV was more uniform and varied between patients by only 9.6% (58.2 to 63.8 Gy), to deliver MED of 56 Gy for α/β - 1. Single course IMRT plan MUs were slightly larger than those for two-course IMRT plans, but within the range seen for two-course plans ( MUs, n=51). Dose max for single-course plans were similar to two-course plans. Doses to PTV, rectum and bladder with single course plans were as per DVC and comparable to two-course plans. Single course IMRT plan reduces IMRT planning and QA time to half. Nandanuri M. S. Reddy, Ph.D. 1 Brij Mohan Sood, M.D. 1,2,* Seshadri Sampath, Ph.D. 1 Andrej Mazur, Ph.D. 1 Adrian Osian, M.S. 1 Akkamma Ravi, M.D. 1,2 Jaganmohan Poli, M.D. 1,2 Dattatreyudu Nori, M.D. 1,2 1 Department of Radiation Oncology The New York Hospital Queens Main Street Flushing, NY 11355, USA 2 Department of Radiation Oncology New York Presbyterian Hospital Weill-Cornell Medical Center 525 East 68 th Street New York, NY 10021, USA Key words: Prostate; Seminal vesicles; IMRT; BED; MED; and LQ model. Introduction IMRT is the closest solution to the central goal of radiation therapy, which is to minimize the dose to the critical normal structures and to escalate the dose to the tumor (1-8). Several publications have shown that this goal is achievable in head and neck, prostate, lung, and breast cases (1-13). Currently, two IMRT techniques are being used to treat prostate and SV. With the conventional two-course techniques, prostate and SV are treated together to a certain dose, followed by a boost to prostate only, with 180 cgy per fraction. With the * Corresponding Author: Brij Mohan Sood, M.D. brijmsood@aol.com Abbreviations: IMRT, Intensity modulated radiation therapy; SC, Single course; SV, Seminal vesicles; CTV, Clinical target volume; PTV, Planning target volume; BED, Biologically effective dose; MED, Matched effective dose; DVC, Dose volume constraints; LQ model, Linear quadratic model. 503

2 504 Reddy et al. simultaneous integrated boost (SIB) technique, prostate is irradiated with hypofractionation (more than 180 cgy per fraction) while the SV or pelvic nodes are irradiated with 180 cgy per fraction (1, 6, 9-13). At our institute, we have treated more than 150 prostate cancer patients with two-course conventional fractionation with IMRT. The first course was to deliver 45 Gy to seminal vesicles (SV) and prostate in 25 fractions at 180 cgy per fraction (14). Second course delivers boost to the prostate with an additional 36 Gy in 20 fractions at 180 cgy per fraction (14). This two-course IMRT needs two IMRT plans and two plan verification QAs. In addition, analysis of dose to SV in 51 patients has shown that SV receives non-uniform dose for a given patient and between patients (45 Gy-80 Gy). We have developed a single course IMRT plan to deliver 81 Gy to prostate in 45 fractions at 180 cgy per fraction and to deliver a Matched Effective dose (MED) to SV in 45 fractions, which in turn has the same biologically effective dose (BED) as that of 45 Gy delivered in 25 fractions at 180 cgy per fraction. MED were calculated for α/β values from 1 to 10. We have used LQ model (15-18) to calculate BED and to derive MED to deliver in 45 fractions, which in turn is equivalent to the 45 Gy to SV in 25 fractions. The BED and MED values were calculated for α/β ranging from 1 to 10. We have applied the newly developed single course IMRT plan retrospectively to 14 patients with varying volumes of SV, rectum, and bladder. Our results show that while delivering the doses to rectum, bladder and prostate similar to those delivered with two-course IMRT plans, a MED dose for any given α/β value can be delivered to SV in 45 fractions. The dose delivered to SV with single course IMRT is more uniform, not only for a given patient but also between patients. In addition, with single course IMRT, the time required for planning and QA is reduced to half because only one IMRT plan and one plan verification QA is required to deliver the prescription dose to SV and prostate. This single course IMRT plan approach may be applicable to other sites with two targets requiring two different prescriptions Methods and Materials Patient Selection All patients, with adenocarcinoma of prostate, with intermediate or high risk were eligible for IMRT. Both prostate and SV were treated. In case of patients with lymph node involvement, whole pelvis was treated with 3D conformal radiotherapy (3DCRT) to 45 Gy, followed by 3DCRT or IMRT boost to prostate only to 30.6 Gy or 36Gy, respectively. Patients were simulated in supine position with alpha cradle immobilization. Fluoroscopy and orthogonal films were used to place isocenter and skin marks. Isocenter was 6 cm posterior to the tip of pubic arch and 1 cm inferior to pubic brim. CT images were obtained with immobilization. Prostate, SV, rectum, bladder, and femoral heads were contoured using the CAT scan images with a separation of 5 mm, for 51 patients. Entire SV were contoured. Whole rectum was contoured from recto-sigmoid flexure to anorectal verge (14). Varian eclipse planning system (Varian Medical Systems Inc., Palo Alto, CA 94304, USA) was used to generate 5-field IMRT plans with DMLC (gantry angles 250, 315, 45, 110, 180). Prescriptions and Margins For two-course IMRT plans, two separate planning target volumes (PTVs) were used: PTV and PPTV (prostate planning target volume). For course 1, prostate + SV = CTV, CTV + margin = PTV. For course 2, prostate + margin = PPTV. Superior and posterior margins for first course (CTV) and second course (prostate only) were 0.5 cm and anterior and inferior margins were 1 cm. First course IMRT prescription to PTV was 45 Gy (prostate and SV) in 25 fractions at 180 cgy per fraction. Second course prescription was 36 Gy to PPTV (prostate) in 20 fractions, at 180 cgy per fraction. For the single-course IMRT plan, a new SV-PTV was created which was: PTV-PPTV. Therefore, the margins for prostate remained the same as that in two-course IMRT plans. However, in the case of SV, the inferior margin was 0. Inferior margin for SV was 0 because the 0.5 cm superior margin for prostate overlaps SV and gives required dose coverage to SV. In single-course IMRT plan, dose volume constraints were placed on PPTV and SV-PTV, separately. Prescription to prostate was 81 Gy in 45 fractions. Prescription to SV was to cover with 95% of any MED value in 45 fractions, (e.g., with 52 Gy in 45 fractions at 1.16 cgy per fraction. The dose-volume constraints (DVC) with IMRT plans was to keep the dose to 30, 50, and 70% of bladder and rectal volumes to less than 70, 60, and 40% of 81 Gy. Acceptable dose to PTVs was to cover 95% of PTVs with at least 95% of prescription dose. Dose to 10, 30, 50, and 70% of rectum and bladder were estimated from the DVH of IMRT plans (14). Calculation of BED and MED Values for SV BED values for α/β values ranging from 1 to 10 were calculated using the LQ model (15-19): BED = nd(1+d/α/β) [1] Where, n = number of fractions, d = dose per fraction. BED for SV, for an α/β value of 3, for two-course IMRT = (1+1.8/α/β) = 72 Gy

3 Single Course IMRT to Treat SV and Prostate to Different Doses 505 From this relationship, the fraction size and the total dose called Matched Effective Dose (MED) for delivering a BED of 72 in 45 fractions has been derived: (1+1.8/α/β) = 45d(1+d/α/β) = 72 Gy 3 [2] Then the total dose, also called MED, to be delivered in 45 fractions to SV, which has a BED of 72 = 45d(1+d/α/β), where, 45 is the number of fractions, d is dose per fraction and α/β = 3. From this equation, the calculated value of d = 1.16 Gy. Then the MED (total dose) that needs to be delivered in 45 fractions = = 52 Gy. In other words, delivering a total dose (MED) of 52 Gy in 45 fractions at 1.16 Gy per fraction has the same biological effectiveness as that of delivering 45 Gy in 25 fractions at 1.8 Gy per fraction, for an α/β value of (1+1.8/α/β) = (1+1.16/α/β) = 72 Gy 3 [3] The dose per fraction and MED required for a given α/β value (1 to 10) have been calculated, which in turn is equal to 45 Gy delivered to SV in 25 fractions at 180 cgy per fraction, using Equations [1]-[3]. We call this as Matched Effective Dose (MED) method, where the BED of two fractionation regimens is the same. This MED method would be useful to create a new fractionation regimen with same BED as that of an existing fractionation regimen and in comparing two or more fractionation regimens in terms of BED, for any given α/β. An example of MED method from the literature may be informative here. The BED for an α/β of 3, for a standard fractionation regimen of delivering 81 Gy in 45 fractions at 1.8 Gy / fraction = Gy 3. The BED for SIB-IMRT with a hypofractionation regimen of delivering 70 Gy in 28 fractions at 2.5 Gy per fraction (1) = Gy 3. Comparison of Single and Two-course IMRT Plan Dosimetry Single course IMRT plans were generated for 14 patients with differing volumes of SV, rectum, and bladder. In addition, single course plans were also generated for MED values for α/β values of 1, 1.5, 3, 5, and 10. These dosimetry parameters for single course IMRT plans were compared with the dosimetric parameters for the two-course plans, for the same patients, retrospectively. In addition, we reviewed data on 51 patients treated with two-course IMRT plans for comparison of MUs, dose max, and SV volumes. Comparison was in terms of dose to SV, MUs, global dose-max, and currently used dose volume constraints (DVC), as described earlier under Prescriptions and Margins. Less than a 5% difference in rectal and bladder doses between single course and two-course IMRT plans implied that single and twocourse IMRT plan doses were comparable. Statistical Analysis Correlation between dose to SV with the increase in the volume of SV with single and two-course plans and between SV volumes and dose to bladder and rectum were analyzed. Linear regression analysis, correlation coefficient r, and two-tailed P values were used to study the correlation between the paired measurements. Results Calculated BED and MED Values The BED and MED values for α/β values ranging from 1-10 are presented in Figure 1. This data also show that the BED values decrease with the increase in the α/β value, as shown by others (6, 18, 19) and so does MED values. MED delivered in 45 fractions to SV has the same BED as that of 45 Gy delivered to SV in 25 fractions, for a given α/β. This means that the biological effectiveness of the total dose to SV in both the fractionation regimens is the same BED MED α/β value Figure 1: Biologically effective dose (BED, squares) and Matched Equivalent Dose (MED, diamonds) for the fractionation regimen of delivering 45 GY in 25 fractions at 180 cgy per fraction to SV, for α/β values ranging from 1 to 10. See Methods and Materials for calculation details. BED and MED Dose to SV with Two-course IMRT Plans Volumes of SV ranged from 2.9 cc to 30 cc (Fig. 2). The mean doses received by SV with two-course treatment are shown in Figure 2. It was seen that the mean doses to SV varied between patients from 54 Gy to 80 Gy. Minimum dose varied from 45.3 to 71 Gy. In addition, it was seen that the dose to SV decreased with the increase in the volume of SV (Fig. 2, P<0.05). This means that smaller the volume of SV, larger was the dose to SV and vice versa (Fig. 2). This reflects the fact that when the SV volume was small, most of the SV was in the PPTV and received a higher dose, as much as 80 Gy, all though the prescription for SV was

4 506 Reddy et al. 45Gy. However, when the volume of SV was large, part or most of it was out side the PPTV and, therefore, received relatively less-dose, although equal to or above the prescribed dose of 45 Gy to SV. Delivering a Dose of 56 Gy to SV with Single Course IMRT Plan 56 Gy is the MED for an α/β of 1.0 (Fig. 1). Dose volume Mean Dose to SV, cgy Mean dose y = x R 2 = SV volume, cc Figure 2: Mean dose delivered to varying volumes of SV with two-course IM. The prescription was 45 Gy in 25 fractions at 180 cgy per fraction to prostate and SV, followed by a boost to prostate to 81 Gy in 45 fractions. Dose to SV decreases with increase in the volume of SV (P<0.05). Minimum and mean dose to SV, cgy Mean dose Minimum dose SV volume, cc Figure 4: Minimum (diamonds) and mean (squares) dose to varying volumes of SV with single-course plans. The prescription was 56 Gy to SV and 81 Gy to prostate in 45 fractions. Dose to SV was independent of SV volume (P>0.2) Figure 3: (A) DVH for SV with a small volume of 2.9 cc observed with twocourse IMRT and single-course IMRT plans. Curve to the left (SC) is for single course and the curve to the right (2C) is for two-course IMRT plans. (B) DVH for SV with a large volume of 29 cc observed with two-course IMRT and single course IMRT plans. Curve to the left is for two-course (2C) and the curve to the right is for single course (SC), IMRT plans. Figure 5: Comparison of isodose distributions for two-course (top) and single-course IMRT (bottom) plans, for the same patient is shown. Magenta, prostate; red, PTV; brown, rectum; and cyan, femurs. Prescription with twocourse plan to SV and prostate was 45 GY (course 1) and 36 Gy to prostate (course 2). Prescription with single-course IMRT plan to SV was 56 Gy (α/β 1) and to prostate was 81 GY. Isodose lines are in absolute dose, cgy.

5 Single Course IMRT to Treat SV and Prostate to Different Doses 507 Table I Dose to 50% bladder, 50% rectum (cgy), and Dose-max, and dose covering 95% of PPTV when different MED doses were prescribed to SV with single-course IMRT plan. The data for 45 Gy is for two-course IMRT. This data is for comparison with the data of single course IMRT, where different doses, as per a given /, were delivered in 45 fractions. In all plans, prescription to prostate was 81 Gy. Volumes in cc: SV-18.3, bladder-172, and rectum / Prescribed Dose to SV cgy Dose to SV, cgy Dose to 50% Min Mean bladder rectum Dose max, % 95% PPTV covered by % of 81Gy? MU histograms for small and large SV volumes with single course IMRT are compared with the DVH with two-course IMRT plans (Fig. 3). The data presented in Figure 3 show that i) SV with small volume received a higher dose compared to SV with larger volume with single course IMRT plan and ii) that the dose to small and large volumes of SV is the same with single course IMRT plan. In addition, the minimum and mean doses to varying volumes of SV are shown in Figure 4, for delivering a dose of 56 Gy. Dose to SV did not decrease with the increase in the volume of SV (P>0.2). Data in Figures 2 and 3 in comparison with the data in Figures 3 and 4 show that a relatively more uniform dose can be delivered to SV, independent of the volumes ranging from 2.9 cc to 30 cc with single course IMRT plan. The variation in minimum and mean dose to SV between patients was 4.6% (52.5 to 54.6 Gy) and 9.6% (58.2 to 63.8), respectively. Dose to SV with single course IMRT plan is although more uniform than that seen with two-course IMRT (Figures 3 and 4), a small fraction of the SV still gets Gy. This is because, the superior border of prostate PTV (PPTV) and the inferior border of SV are the same and the weighting on PPTV was higher than that on SV PTV. The fraction of SV close to the PPTV gets a slightly higher dose than the prescription dose, even though the inferior margin of SV is 0 cm. This may be acceptable in view of the suggestion that there was an approximate 1% risk of SV involvement beyond 2 cm or 60% of SV and that only the proximal cm (approximately 60%) of SV should be included within the CTV (20). Data presented in Table I show that any dose (MED) can be delivered to SV with single course IMRT while keeping doses to PPTV, rectum and bladder as per prescription and DVC. In addition, the data in Table I show that dose maximum and PPTV coverage seen with single-course IMRT (bottom five rows) are comparable to the data with two-course IMRT (top row in the Table I). However, the MUs increased with the increase in the MED dose delivered with single-course IMRT (Table I). Isodose distributions with two-course and single course IMRT plans at isocenter plane are shown in Figure 5 for the same patient. Prescription with two-course plan to SV and prostate was 45 GY (course 1) and 36 Gy to prostate (course 2). Prescription with single-course IMRT plan to SV was 56 Gy (α/β 1) and to prostate was 81 GY. The isodose distribution for these two plans compare well. The dose to SV for this patient was non-uniform with two-course than with single-course IMRT plan (Fig. 3A). Our data suggests that any dose from 47 Gy to 81 Gy can be delivered to a given SV volume with single-course IMRT plan while keeping dose to rectum below the DVC as in the case of two-course IMRT (Fig. 6). First data points to the left of the Figure are shown for two-course IMRT and are for comparison with dose to rectum with single-course IMRT plans delivering doses from 47 to 81 Gy. The same was true in the case of bladder as shown in Figure 7. The dose to bladder was less than the DVC. However, Dose to 10, 30, 50 and 70% rectum % 30% 50% 70% Dose to SV with single course IMRT, Gy Figure 6: Dose to 10, 30, 50, and 70% volume of rectum with two-course IMRT first column of data points to the left. Dose to 10, 30, 50, and 70% volume of rectum when the prescription to SV varied from 47 to 81 Gy and to prostate was 81 Gy with single course IMRT plans all data points to the right of first column. Rectum volume was 68.7 cc and SV volume was 15.1 cc. Diamonds, 10%; squares, 30%; triangles, 50%; and circles, 70% of rectum volume.

6 508 Reddy et al. there is a trend for a slight increase in dose to bladder as the dose to SV was increased. Such a trend was seen in cases where more of the bladder volume was enclosed in the SV PTV volume. In any case, this portion of the dose delivered to the bladder was less than 180 cgy/fraction. If clinically necessary, bladder doses could be further reduced at the expense of dose to rectum and dose coverage to PTV. This would also be the case where SV and prostate were treated to the same dose, e.g Gy (2, 5, 9, 21). Dose to 10, 30, 50 and 70% bladder, cgy When the SV volume is larger in terms of number of CT slices, more of rectum would be included length-wise. This could result in higher dose to rectum and bladder in patients with larger volumes of SV. Mean doses to varying volumes of rectum and bladder when a MED of 56 Gy, for an α/β of 1, was delivered to different volumes of SV with single course IMRT is shown in Table II. Data presented in this table show that the dose to rectum and bladder could be kept to acceptable levels (as per DVC) when a dose of 56 Gy was delivered to varying volumes of SV. 10% 30% 50% 70% Dose to SV with single course IMRT, Gy Figure 7: Dose to 10, 30, 50, and 70% volume of bladder with twocourse IMRT first column of data points to the left. Dose to 10, 30, 50, and 70% volume of bladder when the prescription to SV varied from 47 to 81 Gy and to prostate was 81 Gy with single course IMRT plans all data points to the right of first column. Bladder volume was and SV volume was 15.1 cc. Diamonds, 10%; squares, 30%; triangles, 50%; and circles, 70% of bladder volume. Discussion Two-course IMRT plan is time intensive and requires two IMRT plans and two QA plan checks. In addition, the dose to SV is very non-uniform (Figs. 2 and 3), though the implications of this non-uniform dose to SV are not clearly understood. Single course IMRT plan can reduce the planning and QA time to half, because only one plan is needed to deliver different prescribed doses to the prostate and SV. Therefore, to accomplish this goal, we have used LQ model (4, 6, 7, 9, 19) to derive MED to be delivered to SV in 45 fractions, which in turn is equal to 45 Gy in 25 fractions, for a given α/β. There is not much data available in the literature on growth kinetics and α/β for seminal vesicles. Therefore, tumor growth during the treatment was assumed to be negligible as reported for prostate (20, 22-24) and the α/β values reported for prostate, ranging from 1 to 10 (9, 16, 17, 24-32), were used for deriving the BED and MED for SV. In view of the slow tumor growth (20, 22-24), use of α/β 1 to 3 would be appropriate for SV. The data presented in Figures 5 and 6 and Table I show that any dose from 47 Gy to 81 Gy could be delivered to SV while keeping the doses to bladder and rectum below the DVC. This single-course IMRT plan provides a choice to treat SV with any desired MED, keeping the dose to rectum and bladder with in the DVC. With single-course IMRT, over all treatment time (T) for SV is longer, 45 vs. 25 days. One may apply a correction factor for the increase in the over all treatment time (20 days) to account for cell proliferation and loss of some effectiveness of dose (15, 19, 31). We have not used any correction factor with the assumption that the effectiveness of the MED is not reduced because the cell proliferation and tumor growth in 6-8 weeks is negligible (22-24). With single-course IMRT, two separate PTVs and prescriptions are required to treat SV and prostate. A prescription for SV, for an α/β of 3 based on LQ model, would be written as to deliver 52 Gy in 45 fractions, at 1.16 cgy per fraction to SVPTV. A second prescription will be required to prostate Table II Dose to 50% rectum and 50% bladder, with varying volumes between patients, when 56 Gy was delivered to SV with single-course IMRT plan. This table shows that 56 Gy ( / 1) could be delivered to patients with varying volumes of SV, bladder, and rectum, while the doses to rectum and bladder could be kept as per dosevolume constraints. Volume Of SV, cc Minimum dose to SV, cgy Rectum volume, cc Dose to 50% rectum, cgy Bladder volume, cc Dose to 50% Bladder, cgy Dose Max

7 Single Course IMRT to Treat SV and Prostate to Different Doses 509 (PPTV) to deliver 81 Gy in 45 fractions at 180 cgy per fraction. DVC for bladder and rectum requires keeping doses to 70, 50, and 30% volumes to less than 40, 60, and 70% of 81 Gy. Inverse algorithm would find the fluence and leaf sequences to find a solution to satisfy the DVC for prostate, SV, bladder, and rectum. The data presented in here and by others (1-8) show that this approach is feasible. Single-course IMRT to deliver a given BED to SV is applicable only when SV and prostate are treated to two different doses. The indications for treating the SV in patients with clinically localized cancer are controversial (20, 33, 34). One may treat SV to 78 Gy in high-risk patients, but it may not be necessary for low and intermediate risk patients (10, 11), because seminal vesicle invasion is not associated with a uniformly poor prognosis (11, 33). Not treating SV can reduce the volume of irradiated rectum by 40-50%, and it is suggested for patients with PSA levels <4 and patients with PSA levels 4-10 and a Gleason score of <6 (33, 34). In some cases SV were not treated (10), in other cases SV was treated to a lesser dose than prostate (6, 11-13, 35) and in a few cases both SV and prostate were treated to the same dose (2, 5, 9, 21). In cases where SV and prostate were treated to different doses with two-course IMRT plans (6, 11-13), the dose to SV could be very non-uniform as shown Figures 2 and 3. A practical approach to deliver a more uniform and yet different doses to prostate and SV, where indicated, is to use single course IMRT, as described here. This new approach, single-course IMRT, should be evaluated in terms of plan parameters, such as the dose to normal tissues, dose maximum, PTV coverage, and MUs. In addition, one can evaluate the merits, or lack thereof, of this concept, by comparing retrospectively with the patient dosimetry and plan evaluation parameters. Data presented in Figures 2-7 and Tables I and II, show that the plan evaluation and dosimetry parameters of the single course IMRT plans are very similar to those seen with two-course IMRT. We have reviewed data of 51 patients treated with twocourse IMRT for comparison. The MUs, although were higher for single-course IMRT (Table II), they were within the range seen for two-course IMRT plans to treat SV and prostate, from 549 to 959 MUs (n = 51). Therefore, the single-course IMRT is not only feasible but also reduces planning QA time to half but also delivers a more uniform dose to SV and saves time. Single-course IMRT as described in this report and SIB IMRT (4, 6, 7, 9-12) are two different approaches to achieve the same goal, that is, to use one IMRT plan instead of two plans to treat two different targets to two different prescriptions. SIB IMRT has been suggested for the treatment of locally confined prostate cancer and high-risk prostate cancer involving pelvic nodes (6, 9-12). In the SIB IMRT, pelvic nodes are treated with the conventional fractionation regimen of 180 cgy per fraction to 45 Gy while the prostate is treated with hypofractionation, that is, increased dose per fraction: 2.27 to 3.17 Gy per fraction (1, 6, 10-12). With this techniques, normal tissues such as bladder, urethra, penile bulb, crura and neurovascular bundle (late responding tissues with low α/β), and rectum enclosed in the PTV would also receive a higher dose per fraction and may pose a problem (4, 6). The dose effect relationships reported for these structures are for brachytherapy and conventional external beam dose fractionation (36-39). Therefore, single-course IMRT would be an alternative approach to SIB IMRT when the normal structures enclosed in the PTV volume are of late responding type with low α/β and, therefore, hypofractionation may not be desirable. With single-course IMRT, the prostate is treated with the conventional fraction of 180 cgy per fraction to a total dose of 81 Gy and the SV is treated with a reduced dose per fraction and with an increase in total dose to SV, in 45 fractions (1.16 cgy per fraction to 52 Gy, for an α/β 3). In conventional hyperfractionation, the dose per fraction is smaller, delivered twice a day and the duration of treatment is same or longer (40-42). In single-course IMRT, the overall treatment duration of SV is longer and the dose per fraction is smaller than that of two-course IMRT, and may be termed as hyperfractionation. Because the α/β for prostate could be as low as 1 (9, 16, 17, 24-32), low dose per fraction may not be ideal. However, the radiobiological rationale in using hypofractionation for prostate tumor with low α/β (9, 16, 17, 24-32), and as well as for head and neck and breast tumors with high α/β (3, 6, 7) is not clearly understood. With hypofractionation, late responding normal tissues with low α/β enclosed in the PTV would be at a higher risk for complications. With low dose per fraction to secondary targets (SV), sparing of late responding normal tissues could be better with hyperfractionation (15, 19, 40-44). On going clinical trials might clarify some of these issues in the near future. Conclusions Most institutions have used two-course IMRT plan, to treat prostate and SV to 45 Gy and then to boost the prostate only to 81 Gy, requiring two IMRT plans and two IMRT plan QAs. Single-course IMRT plan described here can deliver 45 Gy equivalent-dose to SV and 81 Gy to prostate in 45 fractions. With this plan, SV receives 116 cgy per fraction (α/β = 3), while the prostate receives a conventional dose of 180 cgy per fraction. Therefore, toxicity to late responding normal tissues may be reduced. Single course IMRT plan delivers a more uniform dose to SV, while the dose to prostate, rectum, and bladder are the same as that of two-course IMRT. The time required by the dosimetrist, physicist, and physician for planning, reviewing, and QA is reduced to half.

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