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British Journal of Radiology (2006) 79, 148-157
© 2006 British Institute of Radiology
doi: 10.1259/bjr/10206556
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Full Paper

A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis

A Hille, MD, N Töws and C F Hess, PhD, MD

Department of Radiotherapy, University of Göttingen, Göttingen, Germany

Correspondence: Dr Andrea Hille, Klinik für Strahlentherapie, Robert-Koch-Str. 40, 37075 Göttingen, Germany.


   Abstract
Top
 Abstract
Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
 References
 
The purpose of the current study was to quantitatively assess differences between irradiation techniques on normal tissue exposure in different clinical target volumes (CTVs) in irradiation of prostate cancer. 14 patients with prostate cancer undergoing external beam radiotherapy were investigated. The prostate and prostate + proximal/entire seminal vesicles were delineated as CTVs. A three-field and two different four-field plans were generated and compared concerning rectum, bladder and femoral head dose–volume histograms (DVHs). The exposure of the rectum exposed to 40–60 Gy was significantly lower for all CTVs with the three-field technique compared with both four-field techniques. The exposure of the rectum to 70 Gy was significantly lower for all CTVs with the weighted four-field technique compared with the unweighted four-field and three-field techniques. The weighted four-field technique was worst in bladder dose sparing for the three CTVs. Comparing the three-field and the unweighted four-field technique for irradiation of the prostate and prostate + entire seminal vesicles, no technique provided a clear advantage or disadvantage in bladder dose sparing. For irradiation of the prostate + proximal seminal vesicles the unweighted four-field technique provided the best bladder dose sparing. Concerning the exposure of the femoral heads, the three-field technique was significantly worse for the three CTVs compared with both four-field techniques. No difference was found between the unweighted and the weighted four-field techniques. In conclusion, none of the studied techniques consistently proved superior in different CTVs in prostate cancer irradiation with respect to sparing all organs at risk. The absolute differences between the three techniques were small and the clinical relevance of these findings is uncertain.


   Introduction
Top
 Abstract
 Introduction
Methods and materials
 Results
 Discussion
 Conclusion
 References
 
Three-dimensional (3D) conformal radiation treatment with the use of individual multileaf collimators (MLCs) has become the standard treatment technique for localized prostate cancer [1–5]. The number of beams and their orientation vary from one department to another. The simplest techniques use three or four fields [2, 4, 6–10], others use techniques with over five fields [11, 12]. However, the published data do not indicate that more sophisticated techniques increase the therapeutic index [13–19]. It is known that rectal toxicity following external beam irradiation of prostate cancer correlates with radiation dose and the percentage of rectal volume included in the intermediate and high dose-volumes [1, 4, 10, 12, 20]. Recently, the impact of inclusion of the seminal vesicles in the clinical target volume (CTV) on rectal dose has been recognized and a risk-adapted CTV with exclusion of seminal vesicles or inclusion of the proximal 2–2.5 cm of the seminal vesicles was suggested to reduce the risk of rectal toxicity [21–24].

Few studies compared different techniques concerning irradiation of the prostate only [3, 14, 18], the prostate + base of the seminal vesicles [19], or the prostate + entire seminal vesicles [14–16]. These studies draw differing conclusions concerning the best irradiation technique, which may partly be due to different definitions of the CTV in these studies. None of these studies investigated systematically whether there is a difference between techniques concerning irradiation of different CTVs of the prostate.

The purpose of the current study was to quantitatively assess the differences between a simple three-field and two different four-field techniques on irradiated normal tissue exposure in irradiation of the prostate only, the prostate + proximal and the entire seminal vesicles. The evaluation was based on three-dimensional treatment planning including dose–volume histograms (DVH). To our knowledge, this is the first prospective systematic analysis for the effect of treatment technique on normal tissue exposure concerning three different CTVs in prostate cancer irradiation.


   Methods and materials
Top
 Abstract
 Introduction
 Methods and materials
Results
 Discussion
 Conclusion
 References
 
14 consecutive patients with localized prostate cancer stage T1–2 undergoing external beam radiotherapy with curative intent to 72 Gy were investigated prospectively. 3D conformal computer-based planning was carried out on CadPlan treatment planning system (Varian, Palo Alto, CA). The prostate (P), the prostate + entire seminal vesicles (PESV), or the prostate + proximal (PPSV) 2–2.5 cm (approximately 60% in longitudinal direction) of the seminal vesicles were taken as CTV and a planning target volume (PTV) margin of 1 cm was added. The definition of the proximal seminal vesicles was taken from the literature [24]. The prostate, the entire and the proximal seminal vesicles were delineated on each axial slice on the planning computer. The external wall of the rectum was contoured. The craniocaudal rectal extension was defined as the first CT slice above the anal verge (caudal border) and the cranial limit was defined as the first slice below the sigmoid flexure. This definition is consistent with definitions reported in the literature [7, 8, 15, 25]. The external wall of the bladder was contoured.

One planning CT scan (5 mm continuing, 5 mm slice) was carried out with patients in supine position and a comfortably filled bladder. Irradiation technique included individual optimization with conformal treatment planning and the use of individual blocks. Nine plans were produced for each of the 14 patients.

Three different irradiation techniques using 20 MV photons were evaluated.

  1. Four-field box technique with equally weighted fields (so-called unweighted four-field technique for simplification);
  2. Four-field box technique with unequal weighted fields (so-called weighted four-field technique for simplification);
  3. Three-field technique with one anterior and two lateral fields with 90° and 270° wedges.

For technique 2 the weight of the ventral field versus dorsal field was 1.3:0.7, and 1:1 for the lateral fields; for 3 it was 1.3:0.85:0.85 with the highest weight for the anterior field. For techniques 2 and 3, minor modification of the beam weights were performed in order to homogenise the dose distribution inside the PTV. Dose was specified according to the ICRU 50 report [26]. For all techniques the reference point for dose specification was the same. Dose was specified at the centre of the treatment field in projection of the central axes. Concerning dose homogeneity, at least 95% of the PTV was covered by 95% of the prescribed dose as minimum. Field size was adjusted to reach this dose homogeneity criterion. Dose calculation included tissue density correction.

To determine the amount of the rectum exposed to ionizing radiation, the percentage of the irradiated rectum to 40 Gy, 50 Gy, 60 Gy and 70 Gy were calculated by the treatment planning system. Several investigations indicate a relationship between DVHs and the development of chronic rectal toxicity [1, 6, 7, 9, 10, 20, 27–31]. The rectal contouring varies from study to study with some investigators outlining the whole rectum, others the rectal wall. Concerning the rectal borders, some studies outline the anatomic rectum, others the rectum over the length of the fields. It is known that there is a high variability of volume fractions of rectal DVHs depending on how the rectal borders are defined, and it is difficult to compare the results of different studies concerning rectal DVHs [32, 33]. Studies analysing either dose–volume relationships of the rectum with or without the craniocaudal definition which we have used in our study, or studies using an identical or similar craniocaudal definition of the whole rectum, are summarized in Table 1Go. The above mentioned values were chosen following the rectal dose constraints given in these publications [6–8, 27–31].


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  		Table 1. Relationship between dose–volume and late rectal toxicity reported in the literature

 
To determine the amount of the bladder exposed to ionizing radiation, the volume of V100 (defined as the percentage of bladder volume receiving 100% of the prescribed dose) and the percentage of the irradiated bladder to 40 Gy, 50 Gy, 60 Gy, 65 Gy and 70 Gy were calculated by the treatment planning system. The data on the tolerance of the bladder to radiation as a function of the irradiated volume is limited. This may be due to a large variation in the bladder DVHs when considering the modifications of the organ due to different filling [9]. The above mentioned values were chosen following the data in the literature about a relationship between bladder toxicity and the irradiated bladder volume [4, 34–37]. The incidence of acute bladder toxicity increased when more than 30% of the bladder received more than 65 Gy [4, 34, 35]. Late complications, such as bladder contracture and volume loss, are described in 5% to 10% at doses of 40 Gy delivered to the majority of the bladder, at doses of 50–65 Gy delivered to about 30% of the bladder volume and at doses of 65–75 Gy applied to below 20% of the bladder volume [36]. Emami et al estimated the TD5/5 to 65 Gy irradiated to the whole bladder, and 66% of the bladder volume irradiated to 80 Gy [37].

To determine the amount of the femoral heads exposed to ionizing radiation the volume of V50 and V100 (defined as the percentage of femoral head volumes receiving at least 50% and 100% of the prescribed dose) were calculated by the treatment planning system. The available data on the dose–effect relationship for femoral heads are also limited [37, 38]. The clearest proposal is that of Emami et al who indicated that a dose of 52 Gy can be given to the whole femoral head with a risk for chronic toxicity in 5 years to be 5%. The V100 value was chosen following Emami et al's study. However, the dose to the whole femoral head is always lower than 52 Gy in practice. Therefore, we additionally estimated the V50 value.

Statistical analysis
Analysis was performed using the program STATISTICA 6.1 (Stat Soft, Palo Alto, CA). To evaluate the statistical significance of differences, Friedman's ANOVA was performed followed by Wilcoxon matched pairs test. Closure principle was used for multiple tests. The level chosen for significance was >0.05.


   Results
Top
 Abstract
 Introduction
 Methods and materials
 Results
Discussion
 Conclusion
 References
 
PTV
The dose distributions in the PTV for all three CTVs were between 99.8% and 102% and typical standard deviations ranged from 1% to 2.5% for all patients and all considered CTVs and techniques.

No statistically significant differences were found between the three techniques for all three CTVs.

Rectum volume
The median volume of the rectum was 84 cm3 (mean value 90 cm3, standard deviation 31 cm3).

Exposure of the rectum with different techniques
The exposure of the rectum to 40–60 Gy was significantly lower for all CTVs with the three-field technique compared with both four-field techniques. The exposure of the rectum to 70 Gy was significantly lower for all CTVs with the weighted four-field technique compared with the unweighted four-field and three-field techniques.

The differences between the rectal volume receiving 40 Gy, 50 Gy, 60 Gy and 70 Gy, respectively, were significant for all three CTVs between the three-field technique and both four-field techniques, and between both four-field techniques.

Details are demonstrated in Table 2Go. The values of 40 Gy, 50 Gy, 60 Gy and 70 Gy for all three techniques are demonstrated graphically for the prostate only in Figure 1Go, for the PPSV in Figure 2Go and for the PESV in Figure 3Go.


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  		Table 2. Mean and median values, standard deviations(SD) and p-values for the whole rectum exposed to 40–70 Gy in different techniques and clinical target volumes (CTVs)

 

Figure 1
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  		Figure 1. Mean values, standard error and standard deviations(SD) for the rectum exposed to 40–70 Gy in irradiation of the prostate only with different treatment techniques.

 

Figure 2
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  		Figure 2. Mean values, standard error and standard deviations(SD) for the rectum exposed to 40–70 Gy in irradiation of the prostate + proximal seminal vesicles with different treatment techniques.

 

Figure 3
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  		Figure 3. Mean values, standard error and standard deviations(SD) for the volumes 50 Gy, 60 Gy and 65 Gy of the rectum in case of irradiation of the prostate + entire seminal vesicles with different treatment techniques.

 
Bladder volume
The median bladder volume was 154 cm3 (mean value 146 cm3, standard deviation 40 cm3).

Exposure of the bladder with different techniques
P
The bladder volume receiving 50 Gy, 60 Gy and 65 Gy, respectively, was significantly higher with the weighted four-field technique compared with both the unweighted four-field and the three-field techniques. The bladder volume receiving 40 Gy was significantly lower with the unweighted four-field technique compared with the weighted four-field technique. No significant difference was found in the bladder volume receiving 40 Gy, 50 Gy, 60 Gy, 65 Gy and 70 Gy, respectively, between the unweighted four-field and the three-field techniques. No significant difference was found in the bladder volume receiving 70 Gy and the proportion of the bladder volume receiving 100% (V100) of the prescribed dose between the three techniques.

PPSV
The bladder volume receiving 40 Gy was significantly higher with the weighted four-field and three-field techniques compared with the unweighted four-field technique. The bladder volume receiving 50 Gy was significantly higher with the weighted four-field technique compared with the three-field technique.

The bladder volume receiving 60 Gy, 65 Gy and 70 Gy, respectively, was significantly higher with the weighted four-field technique compared with both the unweighted four-field and the three-field techniques. Comparing the bladder volume receiving 60 Gy and 65 Gy, respectively, the three-field technique resulted in a significantly lower value for 60 Gy and in no significantly different value for 65 Gy compared with the unweighted four-field technique. Concerning the proportion of the bladder volume receiving 100% (V100) of the prescribed dose, no significant difference was found between the three techniques.

PESV
The bladder volume receiving 40 Gy was significantly higher with the weighted four-field and the three-field techniques compared with the unweighted four-field technique.

The bladder volume receiving 60 Gy was significantly higher with the weighted four-field compared with the three-field technique. The bladder volume receiving 50 Gy and 65 Gy was significantly higher with the weighted four-field technique compared with the unweighted four-field technique. The bladder volume receiving 70 Gy was significantly lower with the three-field technique compared with both the weighted four-field and the unweighted four-field techniques.

The bladder volume receiving 100% (V100) of the prescribed dose was significantly higher with the weighted four-field technique compared with both the unweighted four-field and the three-field techniques. All other values showed no significant differences between the techniques.

Details for the bladder dose exposure for the three CTVs are given in Table 3Go.


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  		Table 3. Mean and median values, standard deviations(SD) and p-values for the radiation exposure to the bladder in different techniques and clinical target volumes (CTVs)

 
Exposure of the femoral head with different techniques
The femoral head DVHs were averaged over the left and right sides to give a single value.

For all three CTVs the radiation dose to the femoral heads was below 50 Gy with all three techniques. The mean V50 and V100 values for all three CTVs were below 53% and 10% of the prescribed dose with the different techniques. Concerning the V50 values, the three-field technique was significantly worse for all CTVs compared with both four-field techniques. No differences were found between the unweighted four-field and the weighted four-field techniques. Concerning the V100 values no significant difference was found for all CTVs between the different techniques.


   Discussion
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
Conclusion
 References
 
Our study shows that none of the studied three-field and four-field techniques consistently proved superior in irradiation of the prostate, prostate + proximal seminal vesicles and prostate + entire seminal vesicles with respect to sparing all organs at risk. Published data do not indicate that more sophisticated techniques increase the therapeutic index [13–19]. Techniques with more than five fields have a very high burden for daily routine treatment planning, and an optimal radiation technique should not only provide the best sparing for all organs at risk (rectum, bladder, femoral heads), but also be safely implemented without undue burden and reduce the risk of any error. For example, simple, and therefore safe, verification by portal imaging during radiation treatment is given with simple radiation fields. For these reasons, a study, investigating only simple radiation techniques was performed.

P
Bedford et al [14] concluded that for irradiation of the prostate only a four-field technique with two oblique anterior and lateral fields would be optimal for rectal sparing. Koswig et al [3] found that, for irradiation of the prostate, only, the best rectal sparing was with a six-field technique. Khoo et al [16] concluded for prostate irradiation, a three-field technique would bring the best rectal sparing with acceptable bladder and femoral head doses. They performed plans with 6 MV photons. We compared in our study a three-field technique with two different four-field techniques using 20 MV photons and the results of Khoo et al [16] concerning rectal dose sparing can be confirmed by our results. Another recently published study investigated three-field techniques versus four-field techniques in irradiation of the prostate only and found that the three-field technique using an anterior and two lateral (270° and 90°) fields with 20 MV photons provides the best rectal protection [18]. This can also be confirmed by our results. The recent study mentioned found no difference between the techniques in bladder exposure and discussed that this may be due to the CTV (prostate only) [18]. Our data indicate that the three-field technique provides, for irradiation of the prostate only, the best rectal dose sparing with no significant differences in bladder dose sparing compared with the unweighted four-field technique. The weighted four-field technique was worst in bladder dose sparing. Concerning the femoral head doses, the three-field technique was worst.

PPSV
Neal et al compared a three-field, four-field and six-field technique for irradiation of the prostate + the base of seminal vesicles [19]. They found no significant differences considering the irradiated volume of the bladder and the rectum. However, they found a better sparing of the rectum with a weighted four-field technique and a better sparing of the bladder with the six-field technique. Our data indicate for irradiation of the prostate + proximal seminal vesicles the three-field technique to be optimum in rectal dose sparing. The weighted four-field technique was worst in bladder dose sparing and the unweighted four-field technique provided a better sparing of the rectum compared with the three-field technique. Concerning the femoral head doses, the three-field technique was worst.

PESV
For irradiation of the prostate + seminal vesicles, several authors compared different techniques and all of these studies conclude that no single technique is superior when considering all organs at risk (rectum, bladder, femoral head). Fiorino et al compared various coplanar techniques for conformal irradiation of the prostate and seminal vesicles [15]. A three-field technique with an anteroposterior and two lateral 30° wedged fields gave the best sparing of the rectum. The bladder was best spared with a six-field technique. The mean dose of the bladder was significantly better against the three-field technique and the four-field technique. However, considering V95, no significant difference was found between the techniques. The unweighted four-field technique gave the worst sparing of the bladder for Fiorino et al. In our study, the weighted four-field technique gave the worst sparing of the bladder.

Bedford et al [14] compared various four-field techniques with a three-field technique which had lateral oblique fields. They concluded that for irradiation of the prostate and prostate + seminal vesicles, four-field techniques with two oblique anterior and lateral fields with individual field wedges for the different CTVs to be optimal for rectal sparing. However, such a technique has a very high burden for daily routine treatment planning. The simple three-field plan in this study with an anterior and two lateral fields using 6 MV photons showed a comparable level with the four-field technique in rectal dose sparing, in case of irradiation of the prostate + entire seminal vesicles. However, the dose to the superficial body and femoral heads was found to be very high [14]. Khoo [16] concluded for both the prostate and seminal vesicles irradiation a three-field technique would bring the best rectal dose sparing with acceptable bladder and femoral head doses. They performed plans with 6 MV photons also, but the superficial body dose was not mentioned. In our study, we compared a three-field technique with two different four-field techniques using 20 MV photons, and the results of Khoo et al [16] concerning rectal dose sparing can be confirmed by our results. The weighted four-field technique was worst in bladder dose sparing. Comparing the unweighted four-field with the three-field technique in bladder dose sparing, no clear advantages or disadvantages were found. Concerning the femoral head doses, the three-field technique was worst.

The studies investigating various techniques draw differing conclusions concerning the best irradiation technique. Some studies, comparing four and three-field techniques concluded the three-field technique to be best in rectal dose sparing [16, 18]. Others did not confirm these results [14, 19]. The reasons for these differing findings are unclear; PTV margins and PTV coverage which have both an impact on radiation exposure of the organs at risk were comparable among these studies and comparable with our study. The different CTVs in theses studies could have been responsible for the different findings, but our study shows for all three CTVs the best rectal dose sparing with the three-field technique. Concerning the bladder dose, the differing conclusions may be due to different bladder fillings which is known to have an impact on bladder DVHs [9]. In most of the studies, only few endpoints concerning dose volume histograms had been chosen and the investigated points were not associated with doses given in dose-constraint studies. Analysing many dose endpoints, as we have done in our study, can lead to unclear, or even conflicting results. This could be an explanation for the differing results compared with our study.

Although the differences between the three techniques were small in our study they were significant, and we conclude from our data that a three-field technique provided the best rectal but the worst femoral dose sparing with inconsistent results regarding the bladder dose sparing for all three CTVs.

Estimated risk for chronic normal tissue exposure
Rectum
To associate the rectal DVHs in our study with an estimated risk for chronic rectal toxicity, the results were compared with studies analysing relationships between dose–volume and rectal toxicity (Table 1Go).

Although the definitions of the rectum differ in some of these studies from our definition, and although the cut-off levels and the resulting risks for chronic rectal toxicity => grade 2 also differ in these studies, we can draw cautious conclusions from our results regarding an estimated risk for chronic rectal toxicity.

The obtained values from the three different techniques were close together. In patients treated with irradiation of the prostate only, the values for the rectum exposure were below 5% for chronic rectal bleeding => grade 2; for irradiation of the prostate + proximal seminal vesicles between 5% and 15%; and for irradiation of the prostate + entire seminal vesicles over 15% with all three techniques. Nevertheless, the three-field technique provided the best rectal dose sparing, except for the rectal volume exposed to 70 Gy. The weighted four-field technique provided a significantly better rectal dose sparing than the unweighted four-field technique.

Whether the small differences between the various techniques would have an impact on chronic rectal toxicity is uncertain. Furthermore, published data suggest increased local control with lower normal toxicity with new technologies such as intensity modulated radiation therapy (IMRT) [39–42]. IMRT allows the increase of dose in part of the prostate while continuing to protect normal tissue. However, until new technologies such as IMRT are introduced as a widespread clinical routine treatment, 3D conformal radiation therapy should be optimized to reduce toxicity while inreasing local control.

Bladder
To estimate the risk for bladder toxicity we tried to compare our data with the clinical relationship between DVHs and the development of bladder toxicity, as reported in the literature [4, 34–37].

The exposed bladder volumes in our study were similar with the three different techniques. The risk of chronic bladder toxicity in our study can be estimated to be less than 5% to 10% in irradiation of the prostate only with all three techniques. In irradiation of the prostate + proximal/entire seminal vesicles, the risk for chronic toxicity can be estimated to be above 10% with all three techniques. For all three CTVs the weighted four-field technique provided the worst bladder dose sparing. Whether the small differences between the various techniques would have an impact on chronic bladder toxicity is uncertain.

Femoral heads
The three-field technique provided the worst radiation exposure to the femoral heads. The differences for the V50 value were significant; for the V100 value no significant difference was found between the techniques for all three CTVs. As the values for the three techniques were below 52 Gy to the whole femoral heads, the risk of chronic toxicity can be estimated to be below 5% in 5 years for the three CTVs [41].


   Conclusion
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
References
 
In conclusion, none of the studied techniques consistently proved superior in different CTVs in prostate cancer irradiation with respect to sparing all the organs at risk. The absolute differences between the three techniques were small and the clinical relevance of these findings remains uncertain.

Received for publication April 11, 2005. Revision received June 10, 2005. Accepted for publication June 21, 2005.


   References
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
 References
 

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