- Email: [email protected]
Rectal dose reduction using three-dimensional conformal radiotherapy for locally advanced prostate cancer: A combination of conformal dynamic-arc and five-static field technique
Radiotherapy and Oncology 90 (2009) 318–324
Contents lists available at ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Prostate radiotherapy
Rectal dose reduction using three-dimensional conformal radiotherapy for locally advanced prostate cancer: A combination of conformal dynamic-arc and five-static field technique Masahiro Sasaoka a,*, Akimasa Nishikawa b, Tomoyuki Futami a, Kouichi Nishida b, Hiroki Miwa b, Kyuuichi Kadoya b a b
Department of Radiology, Ise Municipal Hospital, Ise-City, Japan Department of Radiological Technology, Ise Municipal Hospital, Ise-City, Japan
a r t i c l e
i n f o
Article history: Received 1 August 2008 Received in revised form 27 September 2008 Accepted 4 October 2008 Available online 12 November 2008 Keywords: Prostate cancer Dynamic-arc 3D-CRT Dose escalation Dose–volume histogram Rectal toxicity
a b s t r a c t Background and purpose: The aims of this study are to compare our three-dimensional conformal radiotherapy (3D-CRT) plan using a combination of conformal dynamic-arc and five-static field (DASF) technique with other 3D-CRT plans for prostate cancer, and to estimate whether dose escalation is possible with DASF radiotherapy (DASF-RT). Methods and materials: Twenty patients with prostate cancer were included in this study. For each patient, five different treatment plans including DASF-RT were created to entire prostate and seminal vesicles. Dose distribution and rectal dose–volume histogram (DVH) for each planning technique were compared. Results: In DASF-RT treatment plan, rectum V40, V50, V60, and V70 were 61.6%, 39.6%, 21.4%, and 0.6%, respectively. Compared with four 3D-CRT techniques, DASF-RT technique significantly reduce rectum V50 to V70 without increasing irradiated bladder and femoral head volumes. In addition, in the simulation of dose escalation to 76 Gy, the increase of each rectal dose–volume parameter (V40 to V75) was small enough. However, in dose escalation to 78 Gy, rectum V75 exceeded 5%. Conclusion: DASF-RT technique could significantly reduce rectal volumes receiving 50–70 Gy compared with other 3D-CRT techniques. DASF-RT was safe and feasible for dose escalation to 76 Gy in prostate radiotherapy. Ó 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 318–324
Dose escalation over 70 Gy in prostate radiotherapy improves both biochemical and clinical local control, especially for intermediate- and high-risk patients [1–8]. Rectal toxicity is the major limiting factor in prostate dose escalation, and it is related to the total prescription dose and the volume of the rectum receiving high doses [9–11]. Three-dimensional conformal radiotherapy (3DCRT) is widely available and allows the delivery of high doses to the prostate sparing the surrounding normal tissues. Several 3DCRT approaches [12–17] have been reported, and demonstrate favorable late rectal toxicities compared with those of conventional radiotherapy [18]. More recently, intensity-modulated radiotherapy (IMRT) has allowed the administration of higher doses of radiation to the prostate while limiting the irradiation of bladder and rectum, and it demonstrates the improvement of treatment outcome including late rectal toxicity [18–22].
However, in Japan, IMRT is still a special treatment technique for prostate radiotherapy in the limited institutions at present, because of the difficulties in quality assurance, prolonged planning time, and need of expensive equipments. Therefore, since January 2002, we have performed definitive radiotherapy using a combination of conformal dynamic-arc and five-static field technique (DASF-RT) to reduce irradiated rectal volumes for prostate cancer. The purposes of this study are as follows. The first is to compare dose–volume histograms (DVHs) for planning target volume (PTV), rectum, bladder, and femoral heads between DASF-RT and other 3D-CRT that were previously reported by several investigators. The second is to simulate whether dose escalation is possible with DASF-RT technique. Materials and methods Patients and treatment outline
* Corresponding author. Address: Department of Radiology, Ise Municipal Hospital, 3038 Kusube-Cho, Ise-City, Mie, Japan. E-mail address: [email protected] (M. Sasaoka). 0167-8140/$ - see front matter Ó 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2008.10.008
This planning study included 20 patients treated for prostate cancer from January 2002 to October 2005 at Ise Municipal
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
Hospital. Seventeen patients were T3N0M0 and the remaining three were T2cN0M0 with PSA > 20 mg/ml or Gleason score >7 (UICC, 2002). Neoadjuvant androgen deprivation (AD) and concurrent AD during radiotherapy was added in all patients (median duration of neoadjuvant and concurrent AD: 6.7 months, range from 4.5 to 12 months). The planning CT scan was performed with 5 mm slices, with no contrast medium, in the supine position with knee and heel immobilization system. Patients were asked to full bladder and empty rectum before CT simulation and daily treatment sessions. Clinical target volume (CTV) included entire prostate and seminal vesicles. PTV was created by adding a 10 mm margin to CTV in all directions, except for 5 mm posterior margin. An additional 5 mm margin was added in all directions around PTV to account for the beam penumbra in each treatment field. Rectum, bladder, and femoral heads were defined as organs at risk (OARs). Rectum was contoured from anal verge to recto-sigmoid flexure as a solid organ. Bladder was contoured as a whole organ including the cavity. Femoral heads were also contoured for each patient. The same CTV, PTV, and OARs were used in DASF-RT and compared with 3DCRT. Each treatment plan including DASF-RT was generated by 3Dtreatment planning system (Eclipse: Varian Medical Systems, Palo Alto, CA). All patients were treated with 10 MV photon beams by Clinac 21EX linear accelerator with 120 multileaf collimator (MLC) (Varian Medical Systems, Palo Alto, CA). Prescription dose was 70 Gy in 35 fractions (2 Gy per fraction) at the isocenter following International Commission on Radiation Units and Measurement recommendation [23]. Beam arrangements of DASF-RT technique The forward-planned DASF-RT used six coplanar fields consisting of one conformal dynamic-arc 350° wide (185–175°) with dy-
319
namic modification of the leaves position and five-static fields with MLCs (90°, 110–120°, 180°, 240–250°, and 270°). This conformal dynamic-arc technique with the multi-leaves was dynamically confirmed to PTV for every 2° of the gantry movement. Field beam weightings were principally set at 1.0, 0.15, 0.15, 0.1, 0.15, and 0.15, respectively, and were adjusted to make a better dose distribution and coverage of PTV. Furthermore, three (110–120°, 180°, and 240–250°) of five-static fields were manually designed to shield rectum included in PTV by MLC (using 90° collimator rotation) based on Beam’s Eye View. Beam arrangements of four compared 3D-CRT techniques For comparison with DASF-RT technique, four coplanar 3D-CRT techniques were planned. The first technique consisted of two-lateral conformal dynamic-arc 100° wide (40°–140° and 220°–320°: 2Arc100°-RT) with dynamic MLCs [13,14]. The second consisted of anterior–posterior, posterior–anterior, and two-lateral fields with MLCs (Box-RT) [15,16]. The third consisted of four-oblique conformal fields (RAO 50°, LAO 310°, RPO 130°, and LPO 230°) combined with two-lateral conformal fields (6F-RT) [12]. The fourth consisted of Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy [17] (Box and Arc-RT). Comparison of DVHs and statistical analysis Dose–volume histograms (DVHs) for PTV, rectum, bladder, and femoral heads were calculated for each patient. Those DVH data were summarized to obtain an average DVH for each technique, and then compared between five treatment techniques. For PTV, mean dose (Dmean), dose given to 95% of PTV (PTV-D95), volume receiving at least 95% of prescribed dose (PTV-V95), and homogeneity index (HI: HI = maximum dose in PTV/minimum dose in PTV) were derived from DVHs. For rectum, bladder, and femoral
Fig. 1. Dose distributions for DASF-RT (a), 2Arc100°-RT (b), Box-RT (c), 6F-RT (d), and Box and Arc-RT (e). Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°RT of 24 Gy radiotherapy.
320
Advanced conformal technique for prostate radiotherapy
Table 1 A comparison of PTV dose–volume parameters between DASF-RT technique and four 3D-CRT techniques. Radiotherapy treatment planning techniques Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean dose
101.4 ± 1.9%
100.0.8 ± 8.9% p < 0.05 (p < 0.05)
100.4 ± 1.8% p < 0.05 (p < 0.05)
99.9 ± 1.1% p < 0.01 (p < 0.01)
100.4 ± 1.4% p < 0.05 (N.S.)
PTV-D95
95.7 ± 1.0%
96.5 ± 0.8% p < 0.01 (p < 0.01)
94.0 ± 1.0% p < 0.01 (p < 0.01)
95.0 ± 1.1% N.S. (N.S.)
95.1 ± 0.9% N.S. (N.S.)
PTV-V95
95.8 ± 1.8%
97.3 ± 1.3% N.S. (N.S.)
88.1 ± 4.0% p < 0.01 (p < 0.01)
92.7 ± 2.8% p < 0.01 (p < 0.01)
92.5 ± 2.5% p < 0.01 (p < 0.01)
HI
1.23 ± 0.04
1.11 ± 0.02 p < 0.01 (p < 0.01)
1.19 ± 0.05 p < 0.05 (p < 0.05)
1.11 ± 0.12 p < 0.01 (p < 0.01)
1.16 ± 0.04 p < 0.01 (p < 0.01)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24Gy radiotherapy; SD, standard deviation; D95, dose given to 95% of PTV; V95, PTV receiving at least 95% of prescribed dose 70 Gy; HI, homogeneity index.
heads, dose–volume parameters (Vx: each OAR volume receiving at least X Gy, respectively) were also derived from DVHs. Dose–volume parameters for each treatment plan were compared using two-tailed Student’s t-test and Wilcoxon’s signed-rank test. Differences were considered significant for p values less than 0.05. Results
Fig. 3b and Table 4 show DVH curves, Dmean, V30, V40, V50, and V60 of femoral heads. The Dmean (30.3 ± 3.8 Gy) of DASF-RT technique was significantly lower than those of four compared 3DCRT techniques. And DASF-RT significantly reduced V30 and V40 compared with four other 3D-CRT. In addition, V50 in DASF-RT plan significantly decreased compared with those in 2Arc100°-RT and 6F-RT plans.
The mean PTV was 156.2 ± 30.1 cm3. The mean CTV was 50.3 ± 12.0 cm3. The mean volumes of rectum, bladder, and femoral heads were 61.8 ± 10.6 cm3, 356.4 ± 173.5 cm3, and 126.5 ± 12.2 cm3, respectively. Dose distribution for each treatment technique Dose distribution for each treatment plan including DASF-RT for one of twenty patients is demonstrated in Fig. 1. The treatment plan using DASF-RT technique demonstrated the concave dose distribution that avoided rectum (Fig. 1a). The Dmean, D95, V95, and HI for PTV in each treatment plan are listed in Table 1. The Dmean for PTV had no significant difference between DASF-RT technique and four compared 3D-CRT techniques. The PTV-D95 for DASF-RT was significantly superior to that for Box-RT. The PTV-V95 in DASF-RT plan was superior compared with those in Box-RT, 6F-RT, and Box and Arc-RT plans. However, HI for DASF-RT technique was slightly worse than those for other 3D-CRT techniques. Dose–volume histograms and dose–volume parameters for rectum The rectal DVH curves for all treatment plans are shown in Fig. 2. The comparison of DASF-RT technique and four different 3D-CRT techniques is demonstrated in Table 2. According to Fig. 2, DASF-RT spared more irradiated rectal volumes compared with four other 3D-CRT. Rectum V50 to V70 for DASF-RT were significantly reduced than those for compared four 3D-CRT, except for V70 of 6F-RT. Dose–volume histograms and dose–volume parameters for bladder and femoral heads The DVH curve, Dmean, and V40–70 of bladder in each treatment plan are shown in Fig. 3a and Table 3. DASF-RT technique significantly reduced Dmean, V40, V50, and V60 compared with Box-RT and Box and Arc-RT techniques. However, Dmean and V40–70 had no significant difference between DFAS-RT and four other 3D-CRT.
Fig. 2. PTV (a) and rectum (b) dose–volume histogram (DVH) curves for DASF-RT, 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy.
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
321
Table 2 A comparison of rectal dose–volume parameters between DASF-RT technique and four 3DCRT techniques. Radiotherapy treatment planning techniques Compared planning techniques 2Arc100°-RT Mean ± SD (%)
Box-RT Mean ± SD (%)
6F-RT Mean ± SD (%)
Box and Arc-RT Mean ± SD (%)
V40 61.6 ± 7.3
71.0 ± 8.9 p < 0.01 (p < 0.01)
65.2 ± 10.4 N.S. (N.S.)
74.1 ± 7.5 p < 0.01 (p < 0.01)
69.2 ± 9.5 N.S. (N.S.)
V45 49.1 ± 7.1
64.8 ± 10.0 p < 0.01 (p < 0.01)
53.9 ± 10.8 N.S. (N.S.)
64.7 ± 9.1 p < 0.01 (p < 0.01)
57.9 ± 10.5 p < 0.05 (p < 0.05)
V50 39.6 ± 6.6
57.9 ± 10.5 p < 0.01 (p < 0.01)
47.2 ± 10.8 p < 0.05 (p < 0.05)
51.4 ± 10.2 p < 0.01 (p < 0.01)
49.7 ± 10.7 p < 0.01 (p < 0.01)
V55 31.3 ± 5.8
49.9 ± 10.6 p < 0.01 (p < 0.01)
40.8 ± 10.4 p < 0.01 (p < 0.01)
43.5 ± 10.3 p < 0.01 (p < 0.01)
42.9 ± 10.5 p < 0.01 (p < 0.01)
V60 21.4 ± 4.5
42.6 ± 10.1 p < 0.01 (p < 0.01)
34.7 ± 10.2 p < 0.01 (p < 0.01)
36.0 ± 10.0 p < 0.01 (p < 0.01)
36.1 ± 10.2 p < 0.01 (p < 0.01)
V65 10.4 ± 2.6
32.4 ± 9.3 p < 0.01 (p < 0.01)
26.0 ± 9.2 p < 0.01 (p < 0.01)
26.1 ± 9.0 p < 0.01 (p < 0.01)
26.9 ± 9.4 p < 0.01 (p < 0.01)
V70 0.6 ± 0.5
4.2 ± 5.4 p < 0.05 (p < 0.05)
5.6 ± 5.9 p < 0.01 (p < 0.01)
1.9 ± 3.2 N.S. (N.S.)
4.8 ± 5.4 p < 0.01 (p < 0.01)
DASF-RT Mean ± SD (%)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior– posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD standard deviation; Vx = rectal volume receiving at least X Gy.
Simulation of dose escalation using DASF-RT The changes of rectum and bladder dose–volume parameters by the simulation of dose escalation using DASF-RT technique are demonstrated in Table 5. The simulation of dose escalation to 76 Gy using DASF-RT technique showed small increases of irradiated rectal volumes in the intermediate- and high-dose regions (50–75 Gy). However, in the simulation of dose escalation to 78 Gy, rectum V75 and V40 exceeded 5% and 70%, respectively. 5. Planning time and treatment delivery time For the time of beam arrangement, DASF-RT technique took an additional 1–2 min compared with four other 3D-CRT techniques. Dose calculation time depended on the performance of 3D-treatment planning system. In the plan using only multi-static field technique (i.e. Box-RT, 6F-RT), dose calculation time was approximately 4 min. In DASF-RT plan, that was about 15 min. The plans using twolateral conformal dynamic-arc technique (i.e. 2Arc100°-RT, Box and Arc-RT) had the calculation time of approximately 30 min. The treatment delivery time of DASF-RT technique was longer than those of four compared 3 D-CRT techniques for about 1 min. Discussion This study showed that DASF-RT provided better sparing rectum and femoral heads with small increase in PTV dose when
Fig. 3. Bladder (a) and femoral head (b) dose–volume histogram (DVH) curves for DASF-RT, 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46Gy and boost 2Arc100°-RT of 24Gy radiotherapy.
compared with 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. In particular, DASF-RT technique significantly reduced V50 to V70 for rectum. However, DASF-RT technique did not significantly increase V40 to V60 of bladder compared with four other 3D-CRT techniques. Although dose escalation >70 Gy for prostate cancer contributes to the improvement of treatment outcome in prostate radiotherapy, that is also associated with the increased risk of late rectal toxicity [1,24]. We devised new 3D-CRT technique to reduce irradiated rectal volumes while keeping D95 > 95% and V95 > 95% for PTV when performed dose escalation from 60 to 70 Gy for prostate cancer in 1992. Akazawa et al. [25] showed that the arcing technique was the most effective when treating the conical shape of prostate alone, while a 6-field technique was better when treating the more irregular combined shape of prostate and seminal vesicles. However, it is difficult to generate the concave dose distribution that avoids rectum using only conformal-arc or multi-static field radiotherapy. Generally, in forward-planned radiotherapy, conformal-arc technique increase irradiated rectal volumes, and multi-static field technique shielding rectum by MLCs worsens homogeneity of the dose distribution in PTV. Therefore, to reduce rectal dose and improve homogeneity of dose distribution in PTV, we developed the forward-planned DASF-RT with a combination of one conformal dynamic-arc and five-static field techniques. A characteristic of this technique is to shield the rectum included in PTV with MLCs at three (110–120°, 180°, and 240–250°) of five-static fields to reduce irradiated rectal volumes. As shown in Fig 1a, this planning technique was able to generate the concave distribution that avoided the rectum, and significantly reduced
322
Advanced conformal technique for prostate radiotherapy
Table 3 A comparison of bladder dose–volume parameters between DASF-RT technique and four 3D-CRT techniques. Radiotherapy treatment planning techniques Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean dose
32.1 ± 11.1 Gy
29.4 ± 12.7 Gy N.S. (N.S.)
37.3 ± 10.6 Gy p < 0.01 (p < 0.05)
30.1 ± 12.7 Gy N.S. (N.S.)
34.6 ± 11.1 Gy p < 0.01 (p < 0.05)
V40
35.0 ± 17.8%
34.4 ± 18.8% N.S. (N.S.)
39.2 ± 20.9% p < 0.01 (p < 0.01)
35.3 ± 19.1% N.S. (N.S.)
36.8 ± 19.6% p < 0.05 (p < 0.05)
V50
28.1 ± 15.4%
29.2 ± 16.9% N.S. (N.S.)
31.4 ± 17.6% p < 0.01 (p < 0.01)
29.6 ± 17.4% N.S. (N.S.)
30.7 ± 17.4% p < 0.01 (p < 0.01)
V60
22.2 ± 12.8%
23.9 ± 14.6% N.S. (N.S.)
26.0 ± 15.0% p < 0.01 (p < 0.01)
23.8 ± 14.8% N.S. (N.S.)
24.9 ± 14.6% p < 0.05 (p < 0.05)
V70
9.4 ± 6.6%
2.5 ± 4.3% p < 0.01 (p < 0.01)
11.1 ± 8.2% N.S. (N.S.)
6.5 ± 6.9% N.S. (N.S.)
8.0 ± 6.7% N.S. (N.S.)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD, standard deviation; Vx, bladder volume receiving at least X Gy.
Table 4 A comparison of femoral heads dose–volume parameters between DASF-RT technique and four 3D-CRT techniques.
Table 5 Rectal and bladder dose–volume parameters on simulation of dose escalation using DASF-RT technique.
Radiotherapy treatment planning techniques
Dose escalation simulation
Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean Dose
30.3 ± 3.8 Gy
41.8 ± 3.1 Gy p < 0.01 (p < 0.01)
36.6 ± 4.9 Gy p < 0.01 (p < 0.01)
39.3 ± 3.6 Gy p < 0.01 (p < 0.01)
38.1 ± 3.7 Gy N.S. (N.S.)
V30
49.4 ± 21.6%
92.8 ± 6.7% p < 0.01 (p < 0.01)
83.1 ± 16.6% p < 0.01 (p < 0.01)
90.5 ± 10.5% p < 0.01 (p < 0.01)
84.1 ± 15.8% p < 0.01 (p < 0.01)
V40
8.9 ± 8.5%
57.9 ± 16.3% p < 0.01 (p < 0.01)
39.1 ± 17.2% p < 0.01 (p < 0.01)
44.9 ± 9.1% p < 0.01 (p < 0.01)
47.0 ± 17.1% p < 0.05 (p < 0.05)
V50
0.2 ± 0.3%
14.6 ± 8.8% p < 0.01 (p < 0.01)
0.0% N.S. (N.S.)
22.7 ± 7.8% p < 0.01 (p < 0.01)
0.0% N.S. (N.S.)
V60
0.0%
1.2 ± 1.3% p < 0.05 (p < 0.05)
0.0% N.S. (N.S.)
0.1 ± 0.2% N.S. (N.S.)
0.0% N.S. (N.S.)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD, standard deviation; Vx, femoral heads volume receiving at least X Gy.
rectum V50–V70 except for V70 of 6F-RT technique compared with four other 3D-CRT techniques. In this study, we did not use whole pelvic radiotherapy (WPRT) for locally advanced prostate cancer. The reasons are as follows. At first, the benefit of the pelvic nodal irradiation using WPRT has been controversial to date [26–28]. In the update report of RTOG 94-13, no statistically significant differences were found in progression free survival and overall survival between WPRT with neoadjuvant AD and prostate only radiotherapy with neoadjuvant AD [29]. In addition, Ashman et al. point out that the improvements of local control rates by dose escalation radiotherapy for
Rectum V40 V45 V50 V55 V60 V65 V70 V75 Bladder V40 V50 V60 V65 V70 V75
70 Gy Mean ± SD (%)
74 Gy Mean ± SD (%)
76 Gy Mean ± SD (%)
78 Gy Mean ± SD (%)
61.6 ± 7.3 49.1 ± 7.1 39.6 ± 6.6 31.3 ± 5.8 21.4 ± 4.5 10.4 ± 2.6 0.6 ± 0.5
67.0 ± 7.1 55.0 ± 7.8 44.5 ± 8.0 36.3 ± 7.7 28.2 ± 6.1 18.1 ± 3.2 7.7 ± 1.2
69.2 ± 7.7 57.9 ± 8.6 46.9 ± 8.8 38.5 ± 8.6 30.9 ± 7.5 21.7 ± 4.8 11.6 ± 2.6 1.7 ± 0.4
71.2 ± 7.5 60.7 ± 8.5 49.5 ± 8.9 40.8 ± 8.7 33.3 ± 8.0 25.0 ± 5.8 15.1 ± 3.3 5.3 ± 1.2
35.0 ± 17.8 28.1 ± 15.4 22.2 ± 12.8 18.3 ± 11.0 9.4 ± 6.6 0.1 ± 0.3
37.0 ± 18.3 29.7 ± 16.0 24.2 ± 13.7 21.2 ± 12.3 17.0 ± 10.4 6.8 ± 5.2
37.9 ± 18.6 30.5 ± 16.3 25.0 ± 14.1 22.3 ± 12.8 18.9 ± 11.2 11.9 ± 8.1
38.8 ± 18.8 31.3 ± 16.6 25.8 ± 14.4 23.2 ± 13.3 20.2 ± 11.9 15.4 ± 9.8
Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; SD, standard deviation; Vx, rectal or bladder volume receiving at least X Gy.
prostate cancer have made the relative importance of WPRT for disease control unclear [30]. For the second, WPRT has increased the risk of acute and late gastrointestinal toxicity [31–36]. To the third, neoadjuvant and concurrent AD are added for all patients in our institution. Dose–volume histograms are widely used to evaluate treatment plans and to estimate the risk for toxicity. In radiotherapy at prescription dose 74 Gy or more, many investigators have demonstrated significant correlations between Grade 2 or worse late rectal toxicity rates and rectal volumes receiving >65 Gy, and considered a value of V70 to be most important predictive parameter for rectal bleeding [9,37–42]. Recently, Fiorino et al. [43] reported a new correlation between rectal dose–volume data and late rectal bleeding in patients treated with 3D-CRT at 70 Gy or higher of prescription dose. They suggested the optimal dose–volume constraints for rectum consisted of V40 < 60–70%, V50 < 55%, V60 < 40%, V70 < 25%, and V75 < 5%. Laan et al. [44] also found that the rectum V70 was most predictive for late Grade 2 or worse
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
rectal toxicity when patients were divided into groups according to specific dose–volume thresholds (V40 P 65%, V50 P 55%, V60 P 45%, and V70 P 20%). Therefore, in dose escalation radiotherapy for prostate cancer, we considered that rectum V40, V50, V60, V70, and V75 should be limited to <60–70%, <55%, <40–45%, <20–25%, and <5%, respectively, as the benchmark to keep below frequency of Grade 2 or worse late rectal bleeding 5–10%. The dose escalation studies using 3D-CRT techniques have recently increased not only rectal toxicity but also urinary toxicity [7,8,14,19]. Although several investigators have reported V65 < 30–40%, V70 < 30–50%, V75 < 10% for bladder dose constraints [14,21,45], many studies have failed to demonstrate a clear statistically significant dose–volume relationship to genitourinary toxicity [18,27,46–48]. In our study, irradiated bladder volumes were smaller than published thresholds for bladder in all treatment plans, because of full bladder during CT simulation and daily treatment. In addition, some investigators reported that conformal dynamic-arc radiotherapy increased femoral head dose compared with static field 3D-CRT [13,49]. However, DASF-RT significantly decreased irradiated dose to femoral heads than 3D-CRT with multi-static fields. We consider that a use of conformal-arc technique of a wide angle (i.e. 350°) and a combination of arc and static field techniques contribute to femoral head dose reduction. In this study, DASF-RT significantly spared rectum V50 to V70 in spite of the treatment plan including entire prostate and seminal. And, even in the simulation of dose escalation from 74 to 76 Gy, rectum V40 to V75 were lower compared with the previously published thresholds for Grade 2 or worse late rectal bleeding. However, IMRT technique should be used for dose escalation over 76 Gy, because rectum V75 (5.3 ± 1.2%) had exceeded 5% in the simulation of dose escalation to 78 Gy. In conclusion, DASF-RT was an effective technique to reduce irradiated rectal volumes without time-consuming and expensive modality like IMRT. Furthermore, from a result of dose escalation simulation, this technique was considered to be feasible for dose escalation to 76 Gy in prostate cancer radiotherapy. Conflict of Interest No actual or potential conflicts of interest exist about the publication of this article. References [1] Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:1097–105. [2] Kupelian PA, Buchsbaum JC, Eishaikh MA, Reddy CA, Klein EA. Improvement in relapse-free survival throughout the PSA era in patients with localized prostate cancer treated with definitive radiotherapy: year of treatment an independent predictor of outcome. Int J Radiat Oncol Biol Phys 2003;57:629–39. [3] Peeters ST, Heemsbergen WD, Koper PC, et al. Dose–response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006;24:1990–6. [4] Jereczek-Fossa BA, Orecchia R. Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for non-metastatic prostate cancer. Radiother Oncol 2007;84:197–215. [5] Dearnaley DP, Hall E, Lawewnce D, et al. Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects. Br J Cancer 2005;92:488–98. [6] Dearnaley DP, Sydes MR, Graham JD, et al. Escalation-dose versus standarddose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomized controlled trial. Lancet Oncol 2007;8:475–87. [7] van Tol-Geerdink JJ, Stalmeier PF, Pasker-de Jong PC, et al. Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT. Int J Radiat Oncol Biol Phys 2006;64:534–43. [8] Zietman AL, DeSilvio ML, Slater JD, 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;294:1233–9.
323
[9] Storey MR, Pollack A, Zagars G, Smith L, Antolak J, Rosen I. Complications from radiotherapy dose escalation in prostate cancer: preliminary results of a randomized trial. Int J Radiat Oncol Biol Phys 2000;48:635–42. [10] Kupelian PS, Reddy CA, Klein FA, Willoughby TR. Short-course intensitymodulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life. Int J Radiat Oncol Biol Phys 2001;51:988–93. [11] Tucker SL, Dong L, Cheung R, et al. Comparison of rectal dose-wall histogram versus dose–volume histogram for modeling the incidence of late rectal bleeding after radiotherapy. Int J Radiat Oncol Biol Phys 2004;60:1589–601. [12] Luo C, Yang CC, Narayan S, et al. Use of benchmark dose–volume histograms for selection of the optimal technique between three-dimensional conformal radiation therapy and intensity-modulated radiation therapy in prostate cancer. Int J Radiat Oncol Biol Phys 2006;66:1253–62. [13] Jereczek-Fossa BA, Cattani F, D’Onofrio A, et al. Dose distribution in 3dimensional conformal radiotherapy for prostate cancer: comparison of two treatment techniques (six coplanar fields and two dynamic arcs). Radiother Oncol 2006;81:294–302. [14] Jereczek-Fossa BA, Vavassori A, Fodor C, et al. Dose escalation for prostate cancer using the three-dimensional conformal dynamic arc technique: analysis of 542 consecutive patients. Int J Radiat Oncol Biol Phys 2008;71:784–94. [15] Perez CA, Michalski JM, Purdy JA, Wasserman TH, Williams K, Lockett MA. Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison. Int J Radiat Oncol Biol Phys 2000;47:629–37. [16] van Lin EN, Hoffmann AL, van Kollenburg P, Leer JW, Visser AG. Rectal wall sparing effect of three different endorectal balloons in 3D conformal and MRT prostate radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:565–76. [17] Zhu 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;10:398–404. [18] Dearnaley DP, Khoo VS, Norman AR, et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomized trial. Lancet 1999;353:267–72. [19] Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 2002;53:1111–6. [20] Zelefsky MJ, Fuks Z, Happersett L, et al. Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 2000;55:241–9. [21] Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY. Analysis of biochemical control and prognostic factors in patients treated with either low-dose threedimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;68:1053–8. [22] De Meerleer GO, Fonteyne VH, Vakaet L, et al. Intensity-modulated radiation therapy for prostate cancer: late morbidity and results on biochemical control. Radiother Oncol 2007;82:160–6. [23] International Commission on Radiation Units and Measurements (ICRU). Report 62: Prescribing, recording and reporting photon beam therapy (supplement to ICRU report 50). Bethesda, MD: International Commission on Radiation Units and Measurements: 1999. [24] Hanks GE, Hanlon AL, Pinover WH, Horwitz EM, Price RA, Schultheiss T. Dose selection for prostate cancer patients based on dose comparison and dose response studies. Int J Radiat Oncol Biol Phys 2000;46:823–32. [25] Akazawa PF, Roach 3rd M, Pickett P, et al. Three dimensional comparison of blocked arcs vs. four and six field conformal treatment of the prostate. Radiother Oncol 1996;41:83–8. [26] Zagars GK, von Eschenbach AC, Johnson DE, Oswald MJ. The role of radiation therapy in stages A2 and B adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys 1988;14:701–9. [27] Vargas CE, Galalae R, Demanes J, et al. Lack of benefit of pelvic radiation in prostate cancer patients with a high risk of positive pelvic nodes treated with high-dose radiation. Int J Radiat Oncol Biol Phys 2005;63:1474–82. [28] Asbell SO, Martz KL, Shin KH, et al. Impact of surgical staging in evaluating the radiotherapeuic outcome in RTOG #77-06, a phase III study for T1BnoMo (A2) and T2NoMo (B) prostate carcinoma. Int J Radiat Oncol Biol Phys 1998;40:769–82. [29] Lawton CA, DeSilvio M, Roach III M, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: update analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 2007;69:646–55. [30] Ashman JB, Zelefsky MJ, Hunt MS, Leibel SA, Fuks Z. Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:765–71. [31] Pollack A. A call for more with a desire for less: pelvic radiotherapy with androgen deprivation in the treatment of prostate cancer. J Clin Oncol 2003;21:1899–901. [32] Ennis RD. Uncertainties regarding pelvic radiotherapy for prostate cancer. J Clin Oncol 2004;22:2254–5. [33] Roach 3rd M. In reply [Letter]. J Clin Oncol 2004;22:2255–7. [34] Gallagher MJ, Brereton HD, Rostock RA, et al. A prospective study of treatment techniques to minimize the volume pf pelvic small bowel with reduction of
324
[35]
[36]
[37]
[38]
[39]
[40]
[41]
Advanced conformal technique for prostate radiotherapy acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys 1986;12:1565–73. Shu HK, Lee TT, Vigneauly E, et al. Toxicity following high-dose threedimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer. Urology 2001;57:102–7. Roach M, DeSilvio M, Thomas CR, et al. Progression free survival (PFS) after whole-pelvic (WP) vs. mini-pelvic (MP) or prostate only (PO) radiotherapy (RT): A subset analysis of RTOG 9413, a phase III prospective randomized trial using neoadjuvant and concurrent (N&CHT). Int J Radiat Oncol Biol Phys 2004;60:S264–5 [abstract]. Pollack A, Zagars GK, Smith LG, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904–11. Boersma LJ, van den Brink M, Bruce AM, et al. Estimation of the incidence of late bladder and rectum complications after high-dose (70–78 Gy) conformal radiotherapy for prostate cancer, using dose–volume histograms. Int J Radiat Oncol Biol Phys 1998;41:83–92. Huang EH, Pollack A, Levy L, et al. Late rectal toxicity: dose–volume effects of conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2002;54:1314–21. Fiorino A, Sanguineti G, Cozzarini C, et al. Rectal dose–volume constraints in high-dose radiotherapy of localized prostate cancer. Int J Radiat Oncol Biol Phys 2003;57:953–62. Vargas C, Martinez A, Kestin LL, et al. Dose–volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy. Int J Radiat Oncol Biol Phys 2005;62:1297–308.
[42] Kuban D, Pollack A, Huang E, et al. Hazards of dose escalation in prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:1260–8. [43] Fiorino C, Fellin G, Rancati T, et al. Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: preliminary results of a multicenter prospective study. Int J Radiat Oncol Biol Phys 2008;70:1130–7. [44] van der Laan HP, van den Bergh A, Schilstra C, Vlasman R, Meertens H, Langendik JA. Grading-system-dependent volume effects for late radiationinduced rectal toxicity after curative radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:1138–45. [45] Valicenti RK, Winter K, Cox JD, et al. RTOG 94-06: is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity? Int J Radiat Oncol Biol Phys 2003;57:614–20. [46] Kopper PC, Stroom JC, van Putten WL, et al. Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study. Int J Radiat Oncol Biol Phys 1999;43:727–34. [47] Teh BS, Mai WY, Uhl BM, 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;49:705–12. [48] Nuyttens JJ, Milto S, Rust Pf, Turrisi 3rd AT. Dose–volume relationship for acute side effects during high dose conformal radiotherapy for prostate cancer. Radiother Oncol 2002;64:209–14. [49] Tobler M, Watson G, Laevitt DD. The application of dynamic field shaping and dynamic dose rate control in conformal rotational treatment of the prostate. Med Dosim 2002;27:251–4.
Contents lists available at ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Prostate radiotherapy
Rectal dose reduction using three-dimensional conformal radiotherapy for locally advanced prostate cancer: A combination of conformal dynamic-arc and five-static field technique Masahiro Sasaoka a,*, Akimasa Nishikawa b, Tomoyuki Futami a, Kouichi Nishida b, Hiroki Miwa b, Kyuuichi Kadoya b a b
Department of Radiology, Ise Municipal Hospital, Ise-City, Japan Department of Radiological Technology, Ise Municipal Hospital, Ise-City, Japan
a r t i c l e
i n f o
Article history: Received 1 August 2008 Received in revised form 27 September 2008 Accepted 4 October 2008 Available online 12 November 2008 Keywords: Prostate cancer Dynamic-arc 3D-CRT Dose escalation Dose–volume histogram Rectal toxicity
a b s t r a c t Background and purpose: The aims of this study are to compare our three-dimensional conformal radiotherapy (3D-CRT) plan using a combination of conformal dynamic-arc and five-static field (DASF) technique with other 3D-CRT plans for prostate cancer, and to estimate whether dose escalation is possible with DASF radiotherapy (DASF-RT). Methods and materials: Twenty patients with prostate cancer were included in this study. For each patient, five different treatment plans including DASF-RT were created to entire prostate and seminal vesicles. Dose distribution and rectal dose–volume histogram (DVH) for each planning technique were compared. Results: In DASF-RT treatment plan, rectum V40, V50, V60, and V70 were 61.6%, 39.6%, 21.4%, and 0.6%, respectively. Compared with four 3D-CRT techniques, DASF-RT technique significantly reduce rectum V50 to V70 without increasing irradiated bladder and femoral head volumes. In addition, in the simulation of dose escalation to 76 Gy, the increase of each rectal dose–volume parameter (V40 to V75) was small enough. However, in dose escalation to 78 Gy, rectum V75 exceeded 5%. Conclusion: DASF-RT technique could significantly reduce rectal volumes receiving 50–70 Gy compared with other 3D-CRT techniques. DASF-RT was safe and feasible for dose escalation to 76 Gy in prostate radiotherapy. Ó 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 318–324
Dose escalation over 70 Gy in prostate radiotherapy improves both biochemical and clinical local control, especially for intermediate- and high-risk patients [1–8]. Rectal toxicity is the major limiting factor in prostate dose escalation, and it is related to the total prescription dose and the volume of the rectum receiving high doses [9–11]. Three-dimensional conformal radiotherapy (3DCRT) is widely available and allows the delivery of high doses to the prostate sparing the surrounding normal tissues. Several 3DCRT approaches [12–17] have been reported, and demonstrate favorable late rectal toxicities compared with those of conventional radiotherapy [18]. More recently, intensity-modulated radiotherapy (IMRT) has allowed the administration of higher doses of radiation to the prostate while limiting the irradiation of bladder and rectum, and it demonstrates the improvement of treatment outcome including late rectal toxicity [18–22].
However, in Japan, IMRT is still a special treatment technique for prostate radiotherapy in the limited institutions at present, because of the difficulties in quality assurance, prolonged planning time, and need of expensive equipments. Therefore, since January 2002, we have performed definitive radiotherapy using a combination of conformal dynamic-arc and five-static field technique (DASF-RT) to reduce irradiated rectal volumes for prostate cancer. The purposes of this study are as follows. The first is to compare dose–volume histograms (DVHs) for planning target volume (PTV), rectum, bladder, and femoral heads between DASF-RT and other 3D-CRT that were previously reported by several investigators. The second is to simulate whether dose escalation is possible with DASF-RT technique. Materials and methods Patients and treatment outline
* Corresponding author. Address: Department of Radiology, Ise Municipal Hospital, 3038 Kusube-Cho, Ise-City, Mie, Japan. E-mail address: [email protected] (M. Sasaoka). 0167-8140/$ - see front matter Ó 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2008.10.008
This planning study included 20 patients treated for prostate cancer from January 2002 to October 2005 at Ise Municipal
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
Hospital. Seventeen patients were T3N0M0 and the remaining three were T2cN0M0 with PSA > 20 mg/ml or Gleason score >7 (UICC, 2002). Neoadjuvant androgen deprivation (AD) and concurrent AD during radiotherapy was added in all patients (median duration of neoadjuvant and concurrent AD: 6.7 months, range from 4.5 to 12 months). The planning CT scan was performed with 5 mm slices, with no contrast medium, in the supine position with knee and heel immobilization system. Patients were asked to full bladder and empty rectum before CT simulation and daily treatment sessions. Clinical target volume (CTV) included entire prostate and seminal vesicles. PTV was created by adding a 10 mm margin to CTV in all directions, except for 5 mm posterior margin. An additional 5 mm margin was added in all directions around PTV to account for the beam penumbra in each treatment field. Rectum, bladder, and femoral heads were defined as organs at risk (OARs). Rectum was contoured from anal verge to recto-sigmoid flexure as a solid organ. Bladder was contoured as a whole organ including the cavity. Femoral heads were also contoured for each patient. The same CTV, PTV, and OARs were used in DASF-RT and compared with 3DCRT. Each treatment plan including DASF-RT was generated by 3Dtreatment planning system (Eclipse: Varian Medical Systems, Palo Alto, CA). All patients were treated with 10 MV photon beams by Clinac 21EX linear accelerator with 120 multileaf collimator (MLC) (Varian Medical Systems, Palo Alto, CA). Prescription dose was 70 Gy in 35 fractions (2 Gy per fraction) at the isocenter following International Commission on Radiation Units and Measurement recommendation [23]. Beam arrangements of DASF-RT technique The forward-planned DASF-RT used six coplanar fields consisting of one conformal dynamic-arc 350° wide (185–175°) with dy-
319
namic modification of the leaves position and five-static fields with MLCs (90°, 110–120°, 180°, 240–250°, and 270°). This conformal dynamic-arc technique with the multi-leaves was dynamically confirmed to PTV for every 2° of the gantry movement. Field beam weightings were principally set at 1.0, 0.15, 0.15, 0.1, 0.15, and 0.15, respectively, and were adjusted to make a better dose distribution and coverage of PTV. Furthermore, three (110–120°, 180°, and 240–250°) of five-static fields were manually designed to shield rectum included in PTV by MLC (using 90° collimator rotation) based on Beam’s Eye View. Beam arrangements of four compared 3D-CRT techniques For comparison with DASF-RT technique, four coplanar 3D-CRT techniques were planned. The first technique consisted of two-lateral conformal dynamic-arc 100° wide (40°–140° and 220°–320°: 2Arc100°-RT) with dynamic MLCs [13,14]. The second consisted of anterior–posterior, posterior–anterior, and two-lateral fields with MLCs (Box-RT) [15,16]. The third consisted of four-oblique conformal fields (RAO 50°, LAO 310°, RPO 130°, and LPO 230°) combined with two-lateral conformal fields (6F-RT) [12]. The fourth consisted of Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy [17] (Box and Arc-RT). Comparison of DVHs and statistical analysis Dose–volume histograms (DVHs) for PTV, rectum, bladder, and femoral heads were calculated for each patient. Those DVH data were summarized to obtain an average DVH for each technique, and then compared between five treatment techniques. For PTV, mean dose (Dmean), dose given to 95% of PTV (PTV-D95), volume receiving at least 95% of prescribed dose (PTV-V95), and homogeneity index (HI: HI = maximum dose in PTV/minimum dose in PTV) were derived from DVHs. For rectum, bladder, and femoral
Fig. 1. Dose distributions for DASF-RT (a), 2Arc100°-RT (b), Box-RT (c), 6F-RT (d), and Box and Arc-RT (e). Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°RT of 24 Gy radiotherapy.
320
Advanced conformal technique for prostate radiotherapy
Table 1 A comparison of PTV dose–volume parameters between DASF-RT technique and four 3D-CRT techniques. Radiotherapy treatment planning techniques Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean dose
101.4 ± 1.9%
100.0.8 ± 8.9% p < 0.05 (p < 0.05)
100.4 ± 1.8% p < 0.05 (p < 0.05)
99.9 ± 1.1% p < 0.01 (p < 0.01)
100.4 ± 1.4% p < 0.05 (N.S.)
PTV-D95
95.7 ± 1.0%
96.5 ± 0.8% p < 0.01 (p < 0.01)
94.0 ± 1.0% p < 0.01 (p < 0.01)
95.0 ± 1.1% N.S. (N.S.)
95.1 ± 0.9% N.S. (N.S.)
PTV-V95
95.8 ± 1.8%
97.3 ± 1.3% N.S. (N.S.)
88.1 ± 4.0% p < 0.01 (p < 0.01)
92.7 ± 2.8% p < 0.01 (p < 0.01)
92.5 ± 2.5% p < 0.01 (p < 0.01)
HI
1.23 ± 0.04
1.11 ± 0.02 p < 0.01 (p < 0.01)
1.19 ± 0.05 p < 0.05 (p < 0.05)
1.11 ± 0.12 p < 0.01 (p < 0.01)
1.16 ± 0.04 p < 0.01 (p < 0.01)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24Gy radiotherapy; SD, standard deviation; D95, dose given to 95% of PTV; V95, PTV receiving at least 95% of prescribed dose 70 Gy; HI, homogeneity index.
heads, dose–volume parameters (Vx: each OAR volume receiving at least X Gy, respectively) were also derived from DVHs. Dose–volume parameters for each treatment plan were compared using two-tailed Student’s t-test and Wilcoxon’s signed-rank test. Differences were considered significant for p values less than 0.05. Results
Fig. 3b and Table 4 show DVH curves, Dmean, V30, V40, V50, and V60 of femoral heads. The Dmean (30.3 ± 3.8 Gy) of DASF-RT technique was significantly lower than those of four compared 3DCRT techniques. And DASF-RT significantly reduced V30 and V40 compared with four other 3D-CRT. In addition, V50 in DASF-RT plan significantly decreased compared with those in 2Arc100°-RT and 6F-RT plans.
The mean PTV was 156.2 ± 30.1 cm3. The mean CTV was 50.3 ± 12.0 cm3. The mean volumes of rectum, bladder, and femoral heads were 61.8 ± 10.6 cm3, 356.4 ± 173.5 cm3, and 126.5 ± 12.2 cm3, respectively. Dose distribution for each treatment technique Dose distribution for each treatment plan including DASF-RT for one of twenty patients is demonstrated in Fig. 1. The treatment plan using DASF-RT technique demonstrated the concave dose distribution that avoided rectum (Fig. 1a). The Dmean, D95, V95, and HI for PTV in each treatment plan are listed in Table 1. The Dmean for PTV had no significant difference between DASF-RT technique and four compared 3D-CRT techniques. The PTV-D95 for DASF-RT was significantly superior to that for Box-RT. The PTV-V95 in DASF-RT plan was superior compared with those in Box-RT, 6F-RT, and Box and Arc-RT plans. However, HI for DASF-RT technique was slightly worse than those for other 3D-CRT techniques. Dose–volume histograms and dose–volume parameters for rectum The rectal DVH curves for all treatment plans are shown in Fig. 2. The comparison of DASF-RT technique and four different 3D-CRT techniques is demonstrated in Table 2. According to Fig. 2, DASF-RT spared more irradiated rectal volumes compared with four other 3D-CRT. Rectum V50 to V70 for DASF-RT were significantly reduced than those for compared four 3D-CRT, except for V70 of 6F-RT. Dose–volume histograms and dose–volume parameters for bladder and femoral heads The DVH curve, Dmean, and V40–70 of bladder in each treatment plan are shown in Fig. 3a and Table 3. DASF-RT technique significantly reduced Dmean, V40, V50, and V60 compared with Box-RT and Box and Arc-RT techniques. However, Dmean and V40–70 had no significant difference between DFAS-RT and four other 3D-CRT.
Fig. 2. PTV (a) and rectum (b) dose–volume histogram (DVH) curves for DASF-RT, 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy.
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
321
Table 2 A comparison of rectal dose–volume parameters between DASF-RT technique and four 3DCRT techniques. Radiotherapy treatment planning techniques Compared planning techniques 2Arc100°-RT Mean ± SD (%)
Box-RT Mean ± SD (%)
6F-RT Mean ± SD (%)
Box and Arc-RT Mean ± SD (%)
V40 61.6 ± 7.3
71.0 ± 8.9 p < 0.01 (p < 0.01)
65.2 ± 10.4 N.S. (N.S.)
74.1 ± 7.5 p < 0.01 (p < 0.01)
69.2 ± 9.5 N.S. (N.S.)
V45 49.1 ± 7.1
64.8 ± 10.0 p < 0.01 (p < 0.01)
53.9 ± 10.8 N.S. (N.S.)
64.7 ± 9.1 p < 0.01 (p < 0.01)
57.9 ± 10.5 p < 0.05 (p < 0.05)
V50 39.6 ± 6.6
57.9 ± 10.5 p < 0.01 (p < 0.01)
47.2 ± 10.8 p < 0.05 (p < 0.05)
51.4 ± 10.2 p < 0.01 (p < 0.01)
49.7 ± 10.7 p < 0.01 (p < 0.01)
V55 31.3 ± 5.8
49.9 ± 10.6 p < 0.01 (p < 0.01)
40.8 ± 10.4 p < 0.01 (p < 0.01)
43.5 ± 10.3 p < 0.01 (p < 0.01)
42.9 ± 10.5 p < 0.01 (p < 0.01)
V60 21.4 ± 4.5
42.6 ± 10.1 p < 0.01 (p < 0.01)
34.7 ± 10.2 p < 0.01 (p < 0.01)
36.0 ± 10.0 p < 0.01 (p < 0.01)
36.1 ± 10.2 p < 0.01 (p < 0.01)
V65 10.4 ± 2.6
32.4 ± 9.3 p < 0.01 (p < 0.01)
26.0 ± 9.2 p < 0.01 (p < 0.01)
26.1 ± 9.0 p < 0.01 (p < 0.01)
26.9 ± 9.4 p < 0.01 (p < 0.01)
V70 0.6 ± 0.5
4.2 ± 5.4 p < 0.05 (p < 0.05)
5.6 ± 5.9 p < 0.01 (p < 0.01)
1.9 ± 3.2 N.S. (N.S.)
4.8 ± 5.4 p < 0.01 (p < 0.01)
DASF-RT Mean ± SD (%)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior– posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD standard deviation; Vx = rectal volume receiving at least X Gy.
Simulation of dose escalation using DASF-RT The changes of rectum and bladder dose–volume parameters by the simulation of dose escalation using DASF-RT technique are demonstrated in Table 5. The simulation of dose escalation to 76 Gy using DASF-RT technique showed small increases of irradiated rectal volumes in the intermediate- and high-dose regions (50–75 Gy). However, in the simulation of dose escalation to 78 Gy, rectum V75 and V40 exceeded 5% and 70%, respectively. 5. Planning time and treatment delivery time For the time of beam arrangement, DASF-RT technique took an additional 1–2 min compared with four other 3D-CRT techniques. Dose calculation time depended on the performance of 3D-treatment planning system. In the plan using only multi-static field technique (i.e. Box-RT, 6F-RT), dose calculation time was approximately 4 min. In DASF-RT plan, that was about 15 min. The plans using twolateral conformal dynamic-arc technique (i.e. 2Arc100°-RT, Box and Arc-RT) had the calculation time of approximately 30 min. The treatment delivery time of DASF-RT technique was longer than those of four compared 3 D-CRT techniques for about 1 min. Discussion This study showed that DASF-RT provided better sparing rectum and femoral heads with small increase in PTV dose when
Fig. 3. Bladder (a) and femoral head (b) dose–volume histogram (DVH) curves for DASF-RT, 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined with two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46Gy and boost 2Arc100°-RT of 24Gy radiotherapy.
compared with 2Arc100°-RT, Box-RT, 6F-RT, and Box and Arc-RT. In particular, DASF-RT technique significantly reduced V50 to V70 for rectum. However, DASF-RT technique did not significantly increase V40 to V60 of bladder compared with four other 3D-CRT techniques. Although dose escalation >70 Gy for prostate cancer contributes to the improvement of treatment outcome in prostate radiotherapy, that is also associated with the increased risk of late rectal toxicity [1,24]. We devised new 3D-CRT technique to reduce irradiated rectal volumes while keeping D95 > 95% and V95 > 95% for PTV when performed dose escalation from 60 to 70 Gy for prostate cancer in 1992. Akazawa et al. [25] showed that the arcing technique was the most effective when treating the conical shape of prostate alone, while a 6-field technique was better when treating the more irregular combined shape of prostate and seminal vesicles. However, it is difficult to generate the concave dose distribution that avoids rectum using only conformal-arc or multi-static field radiotherapy. Generally, in forward-planned radiotherapy, conformal-arc technique increase irradiated rectal volumes, and multi-static field technique shielding rectum by MLCs worsens homogeneity of the dose distribution in PTV. Therefore, to reduce rectal dose and improve homogeneity of dose distribution in PTV, we developed the forward-planned DASF-RT with a combination of one conformal dynamic-arc and five-static field techniques. A characteristic of this technique is to shield the rectum included in PTV with MLCs at three (110–120°, 180°, and 240–250°) of five-static fields to reduce irradiated rectal volumes. As shown in Fig 1a, this planning technique was able to generate the concave distribution that avoided the rectum, and significantly reduced
322
Advanced conformal technique for prostate radiotherapy
Table 3 A comparison of bladder dose–volume parameters between DASF-RT technique and four 3D-CRT techniques. Radiotherapy treatment planning techniques Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean dose
32.1 ± 11.1 Gy
29.4 ± 12.7 Gy N.S. (N.S.)
37.3 ± 10.6 Gy p < 0.01 (p < 0.05)
30.1 ± 12.7 Gy N.S. (N.S.)
34.6 ± 11.1 Gy p < 0.01 (p < 0.05)
V40
35.0 ± 17.8%
34.4 ± 18.8% N.S. (N.S.)
39.2 ± 20.9% p < 0.01 (p < 0.01)
35.3 ± 19.1% N.S. (N.S.)
36.8 ± 19.6% p < 0.05 (p < 0.05)
V50
28.1 ± 15.4%
29.2 ± 16.9% N.S. (N.S.)
31.4 ± 17.6% p < 0.01 (p < 0.01)
29.6 ± 17.4% N.S. (N.S.)
30.7 ± 17.4% p < 0.01 (p < 0.01)
V60
22.2 ± 12.8%
23.9 ± 14.6% N.S. (N.S.)
26.0 ± 15.0% p < 0.01 (p < 0.01)
23.8 ± 14.8% N.S. (N.S.)
24.9 ± 14.6% p < 0.05 (p < 0.05)
V70
9.4 ± 6.6%
2.5 ± 4.3% p < 0.01 (p < 0.01)
11.1 ± 8.2% N.S. (N.S.)
6.5 ± 6.9% N.S. (N.S.)
8.0 ± 6.7% N.S. (N.S.)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°-RT, twolateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD, standard deviation; Vx, bladder volume receiving at least X Gy.
Table 4 A comparison of femoral heads dose–volume parameters between DASF-RT technique and four 3D-CRT techniques.
Table 5 Rectal and bladder dose–volume parameters on simulation of dose escalation using DASF-RT technique.
Radiotherapy treatment planning techniques
Dose escalation simulation
Compared planning techniques DASF-RT Mean ± SD
2Arc100°-RT Mean ± SD
Box-RT Mean ± SD
6F-RT Mean ± SD
Box and Arc-RT Mean ± SD
Mean Dose
30.3 ± 3.8 Gy
41.8 ± 3.1 Gy p < 0.01 (p < 0.01)
36.6 ± 4.9 Gy p < 0.01 (p < 0.01)
39.3 ± 3.6 Gy p < 0.01 (p < 0.01)
38.1 ± 3.7 Gy N.S. (N.S.)
V30
49.4 ± 21.6%
92.8 ± 6.7% p < 0.01 (p < 0.01)
83.1 ± 16.6% p < 0.01 (p < 0.01)
90.5 ± 10.5% p < 0.01 (p < 0.01)
84.1 ± 15.8% p < 0.01 (p < 0.01)
V40
8.9 ± 8.5%
57.9 ± 16.3% p < 0.01 (p < 0.01)
39.1 ± 17.2% p < 0.01 (p < 0.01)
44.9 ± 9.1% p < 0.01 (p < 0.01)
47.0 ± 17.1% p < 0.05 (p < 0.05)
V50
0.2 ± 0.3%
14.6 ± 8.8% p < 0.01 (p < 0.01)
0.0% N.S. (N.S.)
22.7 ± 7.8% p < 0.01 (p < 0.01)
0.0% N.S. (N.S.)
V60
0.0%
1.2 ± 1.3% p < 0.05 (p < 0.05)
0.0% N.S. (N.S.)
0.1 ± 0.2% N.S. (N.S.)
0.0% N.S. (N.S.)
p-Value: Student’s t-test (Wilcoxon’s test). Abbreviations: 3D-CRT, three-dimensional conformal radiotherapy; DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; 2Arc100°RT, two-lateral conformal dynamic-arc 100° wide radiotherapy; Box-RT, conformal anterior–posterior, posterior–anterior, and two-lateral field radiotherapy; 6F-RT, four conformal oblique combined two-lateral conformal field radiotherapy; Box and Arc-RT, Box-RT of 46 Gy and boost 2Arc100°-RT of 24 Gy radiotherapy; SD, standard deviation; Vx, femoral heads volume receiving at least X Gy.
rectum V50–V70 except for V70 of 6F-RT technique compared with four other 3D-CRT techniques. In this study, we did not use whole pelvic radiotherapy (WPRT) for locally advanced prostate cancer. The reasons are as follows. At first, the benefit of the pelvic nodal irradiation using WPRT has been controversial to date [26–28]. In the update report of RTOG 94-13, no statistically significant differences were found in progression free survival and overall survival between WPRT with neoadjuvant AD and prostate only radiotherapy with neoadjuvant AD [29]. In addition, Ashman et al. point out that the improvements of local control rates by dose escalation radiotherapy for
Rectum V40 V45 V50 V55 V60 V65 V70 V75 Bladder V40 V50 V60 V65 V70 V75
70 Gy Mean ± SD (%)
74 Gy Mean ± SD (%)
76 Gy Mean ± SD (%)
78 Gy Mean ± SD (%)
61.6 ± 7.3 49.1 ± 7.1 39.6 ± 6.6 31.3 ± 5.8 21.4 ± 4.5 10.4 ± 2.6 0.6 ± 0.5
67.0 ± 7.1 55.0 ± 7.8 44.5 ± 8.0 36.3 ± 7.7 28.2 ± 6.1 18.1 ± 3.2 7.7 ± 1.2
69.2 ± 7.7 57.9 ± 8.6 46.9 ± 8.8 38.5 ± 8.6 30.9 ± 7.5 21.7 ± 4.8 11.6 ± 2.6 1.7 ± 0.4
71.2 ± 7.5 60.7 ± 8.5 49.5 ± 8.9 40.8 ± 8.7 33.3 ± 8.0 25.0 ± 5.8 15.1 ± 3.3 5.3 ± 1.2
35.0 ± 17.8 28.1 ± 15.4 22.2 ± 12.8 18.3 ± 11.0 9.4 ± 6.6 0.1 ± 0.3
37.0 ± 18.3 29.7 ± 16.0 24.2 ± 13.7 21.2 ± 12.3 17.0 ± 10.4 6.8 ± 5.2
37.9 ± 18.6 30.5 ± 16.3 25.0 ± 14.1 22.3 ± 12.8 18.9 ± 11.2 11.9 ± 8.1
38.8 ± 18.8 31.3 ± 16.6 25.8 ± 14.4 23.2 ± 13.3 20.2 ± 11.9 15.4 ± 9.8
Abbreviations: DASF-RT, a combination of conformal dynamic-arc and five-static field radiotherapy; SD, standard deviation; Vx, rectal or bladder volume receiving at least X Gy.
prostate cancer have made the relative importance of WPRT for disease control unclear [30]. For the second, WPRT has increased the risk of acute and late gastrointestinal toxicity [31–36]. To the third, neoadjuvant and concurrent AD are added for all patients in our institution. Dose–volume histograms are widely used to evaluate treatment plans and to estimate the risk for toxicity. In radiotherapy at prescription dose 74 Gy or more, many investigators have demonstrated significant correlations between Grade 2 or worse late rectal toxicity rates and rectal volumes receiving >65 Gy, and considered a value of V70 to be most important predictive parameter for rectal bleeding [9,37–42]. Recently, Fiorino et al. [43] reported a new correlation between rectal dose–volume data and late rectal bleeding in patients treated with 3D-CRT at 70 Gy or higher of prescription dose. They suggested the optimal dose–volume constraints for rectum consisted of V40 < 60–70%, V50 < 55%, V60 < 40%, V70 < 25%, and V75 < 5%. Laan et al. [44] also found that the rectum V70 was most predictive for late Grade 2 or worse
M. Sasaoka et al. / Radiotherapy and Oncology 90 (2009) 318–324
rectal toxicity when patients were divided into groups according to specific dose–volume thresholds (V40 P 65%, V50 P 55%, V60 P 45%, and V70 P 20%). Therefore, in dose escalation radiotherapy for prostate cancer, we considered that rectum V40, V50, V60, V70, and V75 should be limited to <60–70%, <55%, <40–45%, <20–25%, and <5%, respectively, as the benchmark to keep below frequency of Grade 2 or worse late rectal bleeding 5–10%. The dose escalation studies using 3D-CRT techniques have recently increased not only rectal toxicity but also urinary toxicity [7,8,14,19]. Although several investigators have reported V65 < 30–40%, V70 < 30–50%, V75 < 10% for bladder dose constraints [14,21,45], many studies have failed to demonstrate a clear statistically significant dose–volume relationship to genitourinary toxicity [18,27,46–48]. In our study, irradiated bladder volumes were smaller than published thresholds for bladder in all treatment plans, because of full bladder during CT simulation and daily treatment. In addition, some investigators reported that conformal dynamic-arc radiotherapy increased femoral head dose compared with static field 3D-CRT [13,49]. However, DASF-RT significantly decreased irradiated dose to femoral heads than 3D-CRT with multi-static fields. We consider that a use of conformal-arc technique of a wide angle (i.e. 350°) and a combination of arc and static field techniques contribute to femoral head dose reduction. In this study, DASF-RT significantly spared rectum V50 to V70 in spite of the treatment plan including entire prostate and seminal. And, even in the simulation of dose escalation from 74 to 76 Gy, rectum V40 to V75 were lower compared with the previously published thresholds for Grade 2 or worse late rectal bleeding. However, IMRT technique should be used for dose escalation over 76 Gy, because rectum V75 (5.3 ± 1.2%) had exceeded 5% in the simulation of dose escalation to 78 Gy. In conclusion, DASF-RT was an effective technique to reduce irradiated rectal volumes without time-consuming and expensive modality like IMRT. Furthermore, from a result of dose escalation simulation, this technique was considered to be feasible for dose escalation to 76 Gy in prostate cancer radiotherapy. Conflict of Interest No actual or potential conflicts of interest exist about the publication of this article. References [1] Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:1097–105. [2] Kupelian PA, Buchsbaum JC, Eishaikh MA, Reddy CA, Klein EA. Improvement in relapse-free survival throughout the PSA era in patients with localized prostate cancer treated with definitive radiotherapy: year of treatment an independent predictor of outcome. Int J Radiat Oncol Biol Phys 2003;57:629–39. [3] Peeters ST, Heemsbergen WD, Koper PC, et al. Dose–response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006;24:1990–6. [4] Jereczek-Fossa BA, Orecchia R. Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy for non-metastatic prostate cancer. Radiother Oncol 2007;84:197–215. [5] Dearnaley DP, Hall E, Lawewnce D, et al. Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects. Br J Cancer 2005;92:488–98. [6] Dearnaley DP, Sydes MR, Graham JD, et al. Escalation-dose versus standarddose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomized controlled trial. Lancet Oncol 2007;8:475–87. [7] van Tol-Geerdink JJ, Stalmeier PF, Pasker-de Jong PC, et al. Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT. Int J Radiat Oncol Biol Phys 2006;64:534–43. [8] Zietman AL, DeSilvio ML, Slater JD, 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;294:1233–9.
323
[9] Storey MR, Pollack A, Zagars G, Smith L, Antolak J, Rosen I. Complications from radiotherapy dose escalation in prostate cancer: preliminary results of a randomized trial. Int J Radiat Oncol Biol Phys 2000;48:635–42. [10] Kupelian PS, Reddy CA, Klein FA, Willoughby TR. Short-course intensitymodulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life. Int J Radiat Oncol Biol Phys 2001;51:988–93. [11] Tucker SL, Dong L, Cheung R, et al. Comparison of rectal dose-wall histogram versus dose–volume histogram for modeling the incidence of late rectal bleeding after radiotherapy. Int J Radiat Oncol Biol Phys 2004;60:1589–601. [12] Luo C, Yang CC, Narayan S, et al. Use of benchmark dose–volume histograms for selection of the optimal technique between three-dimensional conformal radiation therapy and intensity-modulated radiation therapy in prostate cancer. Int J Radiat Oncol Biol Phys 2006;66:1253–62. [13] Jereczek-Fossa BA, Cattani F, D’Onofrio A, et al. Dose distribution in 3dimensional conformal radiotherapy for prostate cancer: comparison of two treatment techniques (six coplanar fields and two dynamic arcs). Radiother Oncol 2006;81:294–302. [14] Jereczek-Fossa BA, Vavassori A, Fodor C, et al. Dose escalation for prostate cancer using the three-dimensional conformal dynamic arc technique: analysis of 542 consecutive patients. Int J Radiat Oncol Biol Phys 2008;71:784–94. [15] Perez CA, Michalski JM, Purdy JA, Wasserman TH, Williams K, Lockett MA. Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison. Int J Radiat Oncol Biol Phys 2000;47:629–37. [16] van Lin EN, Hoffmann AL, van Kollenburg P, Leer JW, Visser AG. Rectal wall sparing effect of three different endorectal balloons in 3D conformal and MRT prostate radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:565–76. [17] Zhu 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;10:398–404. [18] Dearnaley DP, Khoo VS, Norman AR, et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomized trial. Lancet 1999;353:267–72. [19] Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 2002;53:1111–6. [20] Zelefsky MJ, Fuks Z, Happersett L, et al. Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 2000;55:241–9. [21] Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY. Analysis of biochemical control and prognostic factors in patients treated with either low-dose threedimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;68:1053–8. [22] De Meerleer GO, Fonteyne VH, Vakaet L, et al. Intensity-modulated radiation therapy for prostate cancer: late morbidity and results on biochemical control. Radiother Oncol 2007;82:160–6. [23] International Commission on Radiation Units and Measurements (ICRU). Report 62: Prescribing, recording and reporting photon beam therapy (supplement to ICRU report 50). Bethesda, MD: International Commission on Radiation Units and Measurements: 1999. [24] Hanks GE, Hanlon AL, Pinover WH, Horwitz EM, Price RA, Schultheiss T. Dose selection for prostate cancer patients based on dose comparison and dose response studies. Int J Radiat Oncol Biol Phys 2000;46:823–32. [25] Akazawa PF, Roach 3rd M, Pickett P, et al. Three dimensional comparison of blocked arcs vs. four and six field conformal treatment of the prostate. Radiother Oncol 1996;41:83–8. [26] Zagars GK, von Eschenbach AC, Johnson DE, Oswald MJ. The role of radiation therapy in stages A2 and B adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys 1988;14:701–9. [27] Vargas CE, Galalae R, Demanes J, et al. Lack of benefit of pelvic radiation in prostate cancer patients with a high risk of positive pelvic nodes treated with high-dose radiation. Int J Radiat Oncol Biol Phys 2005;63:1474–82. [28] Asbell SO, Martz KL, Shin KH, et al. Impact of surgical staging in evaluating the radiotherapeuic outcome in RTOG #77-06, a phase III study for T1BnoMo (A2) and T2NoMo (B) prostate carcinoma. Int J Radiat Oncol Biol Phys 1998;40:769–82. [29] Lawton CA, DeSilvio M, Roach III M, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: update analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 2007;69:646–55. [30] Ashman JB, Zelefsky MJ, Hunt MS, Leibel SA, Fuks Z. Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:765–71. [31] Pollack A. A call for more with a desire for less: pelvic radiotherapy with androgen deprivation in the treatment of prostate cancer. J Clin Oncol 2003;21:1899–901. [32] Ennis RD. Uncertainties regarding pelvic radiotherapy for prostate cancer. J Clin Oncol 2004;22:2254–5. [33] Roach 3rd M. In reply [Letter]. J Clin Oncol 2004;22:2255–7. [34] Gallagher MJ, Brereton HD, Rostock RA, et al. A prospective study of treatment techniques to minimize the volume pf pelvic small bowel with reduction of
324
[35]
[36]
[37]
[38]
[39]
[40]
[41]
Advanced conformal technique for prostate radiotherapy acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys 1986;12:1565–73. Shu HK, Lee TT, Vigneauly E, et al. Toxicity following high-dose threedimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer. Urology 2001;57:102–7. Roach M, DeSilvio M, Thomas CR, et al. Progression free survival (PFS) after whole-pelvic (WP) vs. mini-pelvic (MP) or prostate only (PO) radiotherapy (RT): A subset analysis of RTOG 9413, a phase III prospective randomized trial using neoadjuvant and concurrent (N&CHT). Int J Radiat Oncol Biol Phys 2004;60:S264–5 [abstract]. Pollack A, Zagars GK, Smith LG, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904–11. Boersma LJ, van den Brink M, Bruce AM, et al. Estimation of the incidence of late bladder and rectum complications after high-dose (70–78 Gy) conformal radiotherapy for prostate cancer, using dose–volume histograms. Int J Radiat Oncol Biol Phys 1998;41:83–92. Huang EH, Pollack A, Levy L, et al. Late rectal toxicity: dose–volume effects of conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2002;54:1314–21. Fiorino A, Sanguineti G, Cozzarini C, et al. Rectal dose–volume constraints in high-dose radiotherapy of localized prostate cancer. Int J Radiat Oncol Biol Phys 2003;57:953–62. Vargas C, Martinez A, Kestin LL, et al. Dose–volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy. Int J Radiat Oncol Biol Phys 2005;62:1297–308.
[42] Kuban D, Pollack A, Huang E, et al. Hazards of dose escalation in prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:1260–8. [43] Fiorino C, Fellin G, Rancati T, et al. Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: preliminary results of a multicenter prospective study. Int J Radiat Oncol Biol Phys 2008;70:1130–7. [44] van der Laan HP, van den Bergh A, Schilstra C, Vlasman R, Meertens H, Langendik JA. Grading-system-dependent volume effects for late radiationinduced rectal toxicity after curative radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:1138–45. [45] Valicenti RK, Winter K, Cox JD, et al. RTOG 94-06: is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity? Int J Radiat Oncol Biol Phys 2003;57:614–20. [46] Kopper PC, Stroom JC, van Putten WL, et al. Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study. Int J Radiat Oncol Biol Phys 1999;43:727–34. [47] Teh BS, Mai WY, Uhl BM, 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;49:705–12. [48] Nuyttens JJ, Milto S, Rust Pf, Turrisi 3rd AT. Dose–volume relationship for acute side effects during high dose conformal radiotherapy for prostate cancer. Radiother Oncol 2002;64:209–14. [49] Tobler M, Watson G, Laevitt DD. The application of dynamic field shaping and dynamic dose rate control in conformal rotational treatment of the prostate. Med Dosim 2002;27:251–4.