**3. Daily megavoltage CT registration on adaptive Helical Tomotherapy**

In treatments where the organs-at-risk (OARs) are close to the clinical target volume (CTV), the accuracy of the delivered dose is critical. The existence of an accurate patient positioning process is a prerequisite for ensuring agreement between planned and delivered dose distributions (Creutzberg et al. 1993, Mitine et al. 1991). Patient setup inaccuracies can lead to variations in dose delivery and under-dosage of tumors or over-dosage of normal tissues, which can result in a considerable reduction of local tumor control and/or increase of side effects, respectively (Mavroidis et al. 2011).

Helical Tomotherapy (HT) is characterized by dose distributions of high dose conformity (Mackie et al. 1999, Webb 2000). Presently, the Planned Adaptive module of the Tomotherapy software is used to correct dose discrepancies that may occur during treatment delivery. The comparison of the delivered and planned fractional dose distributions can be made in several treatment fractions. To measure the extent of the patient setup deviation on a helical tomotherapy machine, a megavoltage computed tomography (MVCT) scan has been developed for daily correction of patient positioning (Boswell et al. 2006, Meeks et al. 2005, Welsh et al. 2006). Due to the highly conformal distributions that can be obtained with HT any discrepancy between the planned and delivered dose distributions may result in the degradation of the curative power and effectiveness of the treatment (Löf et al. 1995). Consequently, there is a need to measure those differences in terms of a change in the expected clinical outcome. The present analysis performs assessment of the clinical effectiveness of the delivered treatment by interpreting the dosimetric characteristics of the different dose distributions and translating them into expected rates of tumor control and normal tissue complications.

It is worth of noticing that the OAR with the highest risk for complications is rectum in the case of CRT and bladder in the case of IMRT (Fig. 3). This observation confirms previous reports that one of the most important advantages of IMRT over 3D-CRT is the ability of sparing the rectal wall reducing the development of late toxicity. In Fig. 3, it is shown that

For the CRT treatment plans, the response probabilities of CTV and bladder from the CT and fused CT-MRI based treatment plans do not differ significantly (p=0.87 and p=0.49, respectively), whereas those of rectum differ significantly (p=0.02) (Tzikas et al 2011). On the other hand, for the IMRT treatment plans, the response probabilities of all the structures (CTV, bladder and rectum) do not differ significantly between the two sets of plans (p=0.68, p=0.59 and p=0.34, respectively). The improvement that results in by the use of fused CT-MRI images in the overall effectiveness of the CRT plans is statistically significant (p=0.03), which is mainly caused by the statistically significant sparing of the OARs (p=0.03 for *P*I). In the IMRT treatment plans this improvement does not get statistically significant. This stems from the fact that IMRT radiation has to capability of producing highly conformal dose

In the future, target volumes could be reduced by both CT/MRI co-registration and dose painting using MR spectroscopy (Claus et al. 2004, Hou et al. 2009, Scheidler et al. 1999, Weinreb et al. 2009). These ongoing improvements and developments in radiotherapy treatment planning are leading to treatments which offer both better tumour volume coverage, and are minimizing the risk of treatment-related complications (Beasley et al. 2005). These changes should allow the escalation in dose delivered to the tumour volume

the results vary considerably among the patients as indicated by the thin *P*+ lines.

distributions that can spare already from the beginning very well the OARs.

**3. Daily megavoltage CT registration on adaptive Helical Tomotherapy** 

In treatments where the organs-at-risk (OARs) are close to the clinical target volume (CTV), the accuracy of the delivered dose is critical. The existence of an accurate patient positioning process is a prerequisite for ensuring agreement between planned and delivered dose distributions (Creutzberg et al. 1993, Mitine et al. 1991). Patient setup inaccuracies can lead to variations in dose delivery and under-dosage of tumors or over-dosage of normal tissues, which can result in a considerable reduction of local tumor control and/or increase of side

Helical Tomotherapy (HT) is characterized by dose distributions of high dose conformity (Mackie et al. 1999, Webb 2000). Presently, the Planned Adaptive module of the Tomotherapy software is used to correct dose discrepancies that may occur during treatment delivery. The comparison of the delivered and planned fractional dose distributions can be made in several treatment fractions. To measure the extent of the patient setup deviation on a helical tomotherapy machine, a megavoltage computed tomography (MVCT) scan has been developed for daily correction of patient positioning (Boswell et al. 2006, Meeks et al. 2005, Welsh et al. 2006). Due to the highly conformal distributions that can be obtained with HT any discrepancy between the planned and delivered dose distributions may result in the degradation of the curative power and effectiveness of the treatment (Löf et al. 1995). Consequently, there is a need to measure those differences in terms of a change in the expected clinical outcome. The present analysis performs assessment of the clinical effectiveness of the delivered treatment by interpreting the dosimetric characteristics of the different dose distributions and translating them into expected rates of tumor control and

with the potential for increased cure rates.

effects, respectively (Mavroidis et al. 2011).

normal tissue complications.

For each of the examined patients, a Helical Tomotherapy plan was developed and subsequently the calculated dose distributions with and without patient setup correction were compared by using physical and radiobiological measures (Mavroidis et al. 2011). The corresponding cumulative dose distributions, which are determined by adding the delivered fractional dose distributions, are calculated for the entire course of radiation therapy (Fig. 4).

Fig. 4. The reference CT slices of a prostate cancer patient are shown in the transverse and coronal planes for the Helical Tomotherapy dose distributions with (left) and without (right) patient setup correction. In each case, the dose values of the isodose lines are also presented.

In this investigation each patient has a reference kilovoltage CT (kVCT) that was used for the development of the treatment plan. For each fraction, a pre-treatment verification megavoltage CT (MVCT) was obtained in the tomotherapy unit to assess setup accuracy. In order to evaluate the dosimetric effect of setup correction in Helical Tomotherapy, two different cumulative dose distributions were analyzed for the examined clinical cases. One cumulative dose distribution was calculated by adding up the separate delivered fractional dose distributions with setup correction. In this set of merged images, a mutual information based registration (that considered translational and rotational only corrections) was performed between the reference kVCT and the pre-treatment MVCT for each fraction based on anatomical landmarks. The other cumulative dose distribution was computed by adding up the delivered fractional dose distributions as calculated on the daily MVCT, without applying any positional corrections from the daily MVCT-kVCT co-registration. The dose distributions with and without patient repositioning were computed and the final dose volume histograms (DVHs) for both dose calculations were compared (Fig. 5).

Use of Radiobiological Modeling in Treatment Plan

characterizing such a tissue.

dose distribution without setup correction.

Evaluation and Optimization of Prostate Cancer Radiotherapy 245

As it is shown in Fig. 6, the expected complication-free tumor control for the dose distributions with setup correction is equivalent or worse than the delivered dose distributions without setup correction. The reason is that the HT TPS does not have the possibility of performing radiobiological treatment plan optimization, which means that the planned dose distributions could not be produced using the maximum *P*+ as objective. By examining the tumor control and normal tissue complication probabilities separately it can be observed that the dose distributions with setup correction have the same or higher response probabilities than the dose distributions without setup correction. However, for normal tissues the classification of the dose distributions with and without setup correction seems to be more sensitive and it varies depending on the case. In all the cases, the ITV is irradiated almost iso-effectively by the delivered dose distributions with and without patient setup correction. This is supported by the tumor control probabilities, *P*B that are presented in Table 1 (Mavroidis et al. 2011). On the other hand, the setup uncertainties produce higher normal tissue complications when the OARs move into the high dose region

or lower expected responses when the OARs move away from the high dose region.

As far as tissues of parallel internal organizations are concerned, dose inhomogeneity does not affect significantly their response, which is mainly determined by the mean dose. In this case, although the variation of a given dose distribution may be large, the *D* value does not deviate much from the corresponding mean dose, *D* , due to the low relative seriality value

Fig. 6. The dose-response curves that are derived from the radiobiological evaluation of the

indicates the 5-10% response probability region. The solid and dashed vertical lines indicate the dose levels of the dose distributions with and without setup correction, respectively. The vertical error bars indicate the confidence intervals of the corresponding dose-response curves due to the uncertainties of the radiobiological parameters. The solid lines correspond to the dose distribution with setup correction, whereas the dashed lines correspond to the

dose distributions are plotted using *D* on the dose axis. The horizontal crossed bar

Fig. 5. The dose volume histograms (DVHs) of the targets (Prostate, Seminal Vesicles) and organs at risk (bladder, rectum) are illustrated. The solid lines correspond to the dose distribution with setup correction, whereas the dashed lines correspond to the dose distribution without setup correction (Mavroidis et al. 2011) (published with permission from: Mavroidis et al. Radiobiological and dosimetric analysis of daily megavoltage CT registration techniques on adaptive radiotherapy with Helical Tomotherapy. Technology in Cancer Research and Treatment, Vol.10, pp. 9, 2011, Adenine Press, http://www.tcrt.org).

For this dose prescription of the dose distributions with and without setup correction, the complication-free tumor control probabilities, *P* are 10.9% and 11.9% for mean doses to the ITV ( *D*ITV ) of 74.7 Gy and 75.2 Gy and biologically effective uniform doses to the ITV ( *D*<sup>B</sup> ) of 75.2 Gy and 75.4 Gy, respectively. The corresponding total control probabilities, *P*B are 14.5% and 15.3%, whereas the total complication probabilities, *P*I are 3.6% and 3.4%, which are almost equal to the response probabilities of the rectum (3.6% and 3.4%, respectively). At the dose level of the dose distributions with and without setup correction that maximizes the *P*+ index ( *D*ITV = 90.0 Gy), the *P*+ values are 55.9% and 57.7%, respectively.


Table 1. Summary of the radiobiological comparison.

Fig. 5. The dose volume histograms (DVHs) of the targets (Prostate, Seminal Vesicles) and organs at risk (bladder, rectum) are illustrated. The solid lines correspond to the dose distribution with setup correction, whereas the dashed lines correspond to the dose distribution without setup correction (Mavroidis et al. 2011) (published with permission from: Mavroidis et al. Radiobiological and dosimetric analysis of daily megavoltage CT registration techniques on adaptive radiotherapy with Helical Tomotherapy. Technology in Cancer Research and Treatment, Vol.10, pp. 9, 2011, Adenine Press, http://www.tcrt.org). For this dose prescription of the dose distributions with and without setup correction, the complication-free tumor control probabilities, *P* are 10.9% and 11.9% for mean doses to the ITV ( *D*ITV ) of 74.7 Gy and 75.2 Gy and biologically effective uniform doses to the ITV ( *D*<sup>B</sup> ) of 75.2 Gy and 75.4 Gy, respectively. The corresponding total control probabilities, *P*B are 14.5% and 15.3%, whereas the total complication probabilities, *P*I are 3.6% and 3.4%, which are almost equal to the response probabilities of the rectum (3.6% and 3.4%, respectively). At the dose level of the dose distributions with and without setup correction that maximizes

the *P*+ index ( *D*ITV = 90.0 Gy), the *P*+ values are 55.9% and 57.7%, respectively.

**With setup correction** 

**GTV (%)** 15.5 + 0.8 85.2 - 1.0 **Seminal Vesicles (%)** 93.6 + 0.2 99.5 0.0 **Bladder (%)** 0.1 0.0 5.1 - 0.3 **Rectum (%)** 3.6 - 0.2 25.0 - 2.6 *P***+ (%) 10.9 + 1.0 55.9 + 1.8**  *P***B (%) 14.5 + 0.8 84.7 - 1.0**  *P***I (%) 3.6 - 0.2 28.8 - 2.8**  *D*ITV **(Gy) 74.7 + 0.5 90.0 0.0**  *D*B **(Gy) 75.2 + 0.2 90.6 - 0.4** 

**Clinical Dose Prescription Optimum Dose** 

**W/o setup correction**  **Prescription** 

**W/o setup correction** 

**With setup correction** 

**Response probability** 

Table 1. Summary of the radiobiological comparison.

As it is shown in Fig. 6, the expected complication-free tumor control for the dose distributions with setup correction is equivalent or worse than the delivered dose distributions without setup correction. The reason is that the HT TPS does not have the possibility of performing radiobiological treatment plan optimization, which means that the planned dose distributions could not be produced using the maximum *P*+ as objective. By examining the tumor control and normal tissue complication probabilities separately it can be observed that the dose distributions with setup correction have the same or higher response probabilities than the dose distributions without setup correction. However, for normal tissues the classification of the dose distributions with and without setup correction seems to be more sensitive and it varies depending on the case. In all the cases, the ITV is irradiated almost iso-effectively by the delivered dose distributions with and without patient setup correction. This is supported by the tumor control probabilities, *P*B that are presented in Table 1 (Mavroidis et al. 2011). On the other hand, the setup uncertainties produce higher normal tissue complications when the OARs move into the high dose region or lower expected responses when the OARs move away from the high dose region.

As far as tissues of parallel internal organizations are concerned, dose inhomogeneity does not affect significantly their response, which is mainly determined by the mean dose. In this case, although the variation of a given dose distribution may be large, the *D* value does not deviate much from the corresponding mean dose, *D* , due to the low relative seriality value characterizing such a tissue.

Fig. 6. The dose-response curves that are derived from the radiobiological evaluation of the dose distributions are plotted using *D* on the dose axis. The horizontal crossed bar indicates the 5-10% response probability region. The solid and dashed vertical lines indicate the dose levels of the dose distributions with and without setup correction, respectively. The vertical error bars indicate the confidence intervals of the corresponding dose-response curves due to the uncertainties of the radiobiological parameters. The solid lines correspond to the dose distribution with setup correction, whereas the dashed lines correspond to the dose distribution without setup correction.

Use of Radiobiological Modeling in Treatment Plan

Evaluation and Optimization of Prostate Cancer Radiotherapy 247

Fig. 7. The reference CT slice of a prostate cancer patient is shown for the treatment plans of four radiation modalities in the transverse and coronal planes. The anatomical structures involved are illustrated together with the dose distributions delivered to the patient.

Tissue GTV Lymph nodes Bladder Rectum Helical Tomotherapy

*P*Tomo (%) 39.3 98.0 1.0 2.9

*D*Tomo (Gy) 74.8 74.8 61.6 59.6

*D*Tomo (Gy) 74.9 74.8 39.7 34.8 SDTomo 0.9 0.5 20.6 17.6

*D*maxTomo 78.3 77.9 77.9 77.9

*D*minTomo 71.2 73.2 8.3 6.7

*P*IMRT (%) 44.1 98.4 1.4 1.3

*D*IMRT (Gy) 75.6 75.9 62.1 57.7

*D*IMRT (Gy) 75.6 75.9 41.8 34.3 SDIMRT 0.7 0.3 20.2 16.1

*D*maxIMRT 77.5 77.1 76.7 74.7

*D*minIMRT 72.8 74.7 7.9 4.4

treatment plans.

Table 2. Summary of the radiobiological evaluation of the Helical Tomotherapy and IMRT

MLC-based IMRT

In Fig. 6, the clinically established dose prescription (solid and dashed vertical lines), deviates from the optimal dose level that is indicated by the radiobiological evaluation. With a small increase in the dose prescription an increase in the complication-free tumor control, *P*+ can be achieved because the gain in tumor control is larger than the increment in normal tissue complications until a balance is reached. The dashed vertical line indicates the dose prescription, which intersects with the total complication probability of 10%. Because of these points the clinically prescribed dose level is lower than the optimum level by a *D* of about 15.0 Gy.

In the DVH diagram (Fig. 5) it is observed that a significantly higher dose is delivered to the ITV compared to the OARs, which leads to response curves that are well separated from those of the targets as shown in Fig. 6. The width of the *P*+ curve expresses the separation between the response curves of the targets and those of the OARs. At the same time, the most effective dose distribution is indicated, since it generates a higher value of *P*+. The more conformal a treatment technique is the more precise and accurate the patient setup process should be. In these techniques the dose distribution is so well matched with the radiosensitivity map of the clinical case that a small misalignment in the setup can rapidly reduce the effectiveness of the delivered therapy. The quality of a treatment does not only depend on the conformity of the applied technique but also on the quality of the supporting services.

### **4. Radiobiological evaluation of Helical Tomotherapy and MLC-based IMRT treatment plan**

Helical Tomotherapy (HT) is a radiation modality that is capable of producing high conformity dose distributions that may be superior than other IMRT techniques (Mackie et al. 1999, Webb 2000). A unique radiation delivery method is employed by HT, which delivers radiation helically through fifty-one projections per rotation. Although HT can produce very conformal dose distributions, it is still unknown how much the effectiveness of the resulted dose distributions differs from that of other radiation therapy modalities such as that of the MLC-based step-and-shoot IMRT. Consequently, the goal of this analysis is to compare IMRT treatment plans generated using MLC-based step-and-shoot IMRT and HT technology based on radiobiological measures, using representative prostate cancer cases. For each case, two sets of treatment plans have been developed (IMRT and HT). A parallel physical and radiobiological evaluation was carried out to assess the different treatment plans. The implemented radiobiological procedure estimates the probability to achieve tumour control without complications based on the knowledge of the dose-response relations of the tumours and organs-at-risk (Emami et al. 1991, Mavroidis et al. 2003, 2005, Ågren 1995).

Fig. 7 illustrates the dose distributions of a conventional, a conformal (CRT), an MLCbased IMRT and a HT treatment plan, of a prostate cancer case, in the form of isodose curves in transverse and coronal views, respectively (Mavroidis et al. 2007). According to the isodose curve distributions, it appears that the HT plan produces slightly lower inhomogeneity inside the ITV as compared to the MLC-based IMRT and very similar dose spread outside the ITV. The MLC-based IMRT radiation modality delivers higher mean doses to the GTV, lymph nodes and bladder and a lower dose to the rectum as compared to the HT (Table 2).

In Fig. 6, the clinically established dose prescription (solid and dashed vertical lines), deviates from the optimal dose level that is indicated by the radiobiological evaluation. With a small increase in the dose prescription an increase in the complication-free tumor control, *P*+ can be achieved because the gain in tumor control is larger than the increment in normal tissue complications until a balance is reached. The dashed vertical line indicates the dose prescription, which intersects with the total complication probability of 10%. Because of these points the clinically prescribed dose level is lower than the optimum level by a *D* of

In the DVH diagram (Fig. 5) it is observed that a significantly higher dose is delivered to the ITV compared to the OARs, which leads to response curves that are well separated from those of the targets as shown in Fig. 6. The width of the *P*+ curve expresses the separation between the response curves of the targets and those of the OARs. At the same time, the most effective dose distribution is indicated, since it generates a higher value of *P*+. The more conformal a treatment technique is the more precise and accurate the patient setup process should be. In these techniques the dose distribution is so well matched with the radiosensitivity map of the clinical case that a small misalignment in the setup can rapidly reduce the effectiveness of the delivered therapy. The quality of a treatment does not only depend on the conformity of the applied technique but also on the quality of the supporting

**4. Radiobiological evaluation of Helical Tomotherapy and MLC-based IMRT** 

Helical Tomotherapy (HT) is a radiation modality that is capable of producing high conformity dose distributions that may be superior than other IMRT techniques (Mackie et al. 1999, Webb 2000). A unique radiation delivery method is employed by HT, which delivers radiation helically through fifty-one projections per rotation. Although HT can produce very conformal dose distributions, it is still unknown how much the effectiveness of the resulted dose distributions differs from that of other radiation therapy modalities such as that of the MLC-based step-and-shoot IMRT. Consequently, the goal of this analysis is to compare IMRT treatment plans generated using MLC-based step-and-shoot IMRT and HT technology based on radiobiological measures, using representative prostate cancer cases. For each case, two sets of treatment plans have been developed (IMRT and HT). A parallel physical and radiobiological evaluation was carried out to assess the different treatment plans. The implemented radiobiological procedure estimates the probability to achieve tumour control without complications based on the knowledge of the dose-response relations of the tumours and organs-at-risk (Emami et al. 1991, Mavroidis et al. 2003, 2005,

Fig. 7 illustrates the dose distributions of a conventional, a conformal (CRT), an MLCbased IMRT and a HT treatment plan, of a prostate cancer case, in the form of isodose curves in transverse and coronal views, respectively (Mavroidis et al. 2007). According to the isodose curve distributions, it appears that the HT plan produces slightly lower inhomogeneity inside the ITV as compared to the MLC-based IMRT and very similar dose spread outside the ITV. The MLC-based IMRT radiation modality delivers higher mean doses to the GTV, lymph nodes and bladder and a lower dose to the rectum as compared

about 15.0 Gy.

services.

**treatment plan** 

Ågren 1995).

to the HT (Table 2).

Fig. 7. The reference CT slice of a prostate cancer patient is shown for the treatment plans of four radiation modalities in the transverse and coronal planes. The anatomical structures involved are illustrated together with the dose distributions delivered to the patient.


Table 2. Summary of the radiobiological evaluation of the Helical Tomotherapy and IMRT treatment plans.

Use of Radiobiological Modeling in Treatment Plan

distribution from IMRT.

volume(s) and organs at risk (OARs).

**implants** 

Evaluation and Optimization of Prostate Cancer Radiotherapy 249

modalities have almost the same potential of producing treatment plans with small integral

Fig. 9. The dose-response curves of the targets and organs-at-risk are plotted for the HT and MLC-based IMRT radiation modalities using the *D* on the dose axis. The vertical lines denote the clinical and optimum dose prescriptions. The solid lines correspond to the dose distribution from Helical Tomotherapy, whereas the dashed lines correspond to the dose

**5. Radiobiological evaluation of optimized HDR prostate brachytherapy** 

High Dose Rate (HDR) Brachytherapy is becoming popular for treating localized prostate cancer tumors utilizing 3D ultrasound (U/S) and 192Ir based remote afterloaders. Compared to other 3D imaging modalities (CT, MR) U/S can provide real-time, accurate 3D information on the size and the position of the target volume, on the position of the organs-at-risk and the real time needle tracking and navigation. The use of inverse planning in HDR brachytherapy results in a fast planning process that produces reproducible high quality treatment plans that closely match the clinical protocol constraints (Baltas & Zamboglou 2006, Hsu et al. 2008, Martinez et al. 1989, Milickovic et al. 2002). During the last decade a number of inverse planning algorithms have been proposed (Alterovitz et al. 2006, Karabis et al. 2009, Lahanas et al. 1999, 2003) and many of them have been implemented in modern Treatment Planning Systems (TPS) (Oncentra Prostate™, Nucletron B.V., Veenendaal, The Netherlands, Oncentra Brachy™, Nucletron B.V., Veenendaal, The Netherlands, BrachyVision Treatent Planning™, Varian Medical Systems). It is a common characteristic for HDR implants optimized with such algorithms that there are a few very dominating dwell positions, where the largest part of the total dwell time is spent, which leads to a selective extension of high doses in volumes around such dwell positions. Presently, in HDR brachytherapy, new inverse optimization algorithms enable an adjustment of the source dwell time distribution within the implanted catheters according to user-defined objectives and penalties for the target

doses to the healthy organs and fairly homogeneous doses to the ITV.

For the applied dose prescription the complication-free tumor control probability (*P*+) value is 34.7% for the HT for a mean dose to the ITV ( *D*ITV ) of 74.9 Gy and biologically effective uniform dose to the ITV ( *D*<sup>B</sup> ) of 74.8 Gy. The total control probability (*P*B) is 38.5% and the total complication probability (*P*I) is 3.8%. Similarly, of the MLC-based IMRT the *P*<sup>+</sup> value is 40.8% for *D*ITV = 75.7 Gy and *D*<sup>B</sup> = 75.6 Gy. The *P*B = 43.4% and the *P*I = 2.6% (Mavroidis et al 2007). However, if we optimize the dose level of the dose distributions in order to maximize the complication-free tumor control then for the HT, the *P*+ value becomes 68.7% for a *D*B of 86.0 Gy stemming from *P*B = 87.8% and *P*I = 19.1%. Respectively, for the MLC-based IMRT the *P*+ value becomes 72.2% for a *D*B of 85.9 Gy having *P*B = 87.8% and *P*I = 15.5%.

Fig. 8. The DVHs of the GTV and involved lymph nodes as well as those of the organs at risk (bladder and rectum) are illustrated. The solid lines correspond to the dose distribution from Helical Tomotherapy, whereas the dashed lines correspond to the dose distribution from IMRT (Mavroidis et al. 2007) (published with permission from: Mavroidis et al. Treatment plan comparison between Helical Tomotherapy and MLC-based IMRT using radiobiological measures. Physics in Medicine and Biology, Vol.52, pp. 3829, 2007, IOP Publishing Ltd, http://stacks.iop.org/PMB/52/3817).

The dose distribution in the ITV is more homogeneous in the MLC-based IMRT plan as compared to the HT, while achieving a similar sparing of the OARs. As it is shown in Fig. 9, the expected complication-free tumour control for the HT treatment plan is slightly worse than the MLC-based IMRT for the clinical prescribed doses. The reason for this is that the MLC-based IMRT irradiates more effectively the GTV and lymph nodes with better sparing of the rectum as shown in Table 2 and Fig. 9. Although the HT delivers similar mean dose to the rectum with a little larger variation as compared to the MLC-based IMRT, it shows a higher complication probability due to its higher maximum dose and the high relative seriality value of rectum (*s* = 0.7).

In this analysis, the clinical effectiveness of the Helical Tomotherapy and MLC-based IMRT in prostate cancer radiotherapy was evaluated using both physical and radiobiological criteria. This evaluation shows that the difference between the HT and MLC-based IMRT plans is small with the latter one being more effective over the clinically prescribed dose region. The results of this work indicate that the HT and MLC-based IMRT radiation

For the applied dose prescription the complication-free tumor control probability (*P*+) value is 34.7% for the HT for a mean dose to the ITV ( *D*ITV ) of 74.9 Gy and biologically effective uniform dose to the ITV ( *D*<sup>B</sup> ) of 74.8 Gy. The total control probability (*P*B) is 38.5% and the total complication probability (*P*I) is 3.8%. Similarly, of the MLC-based IMRT the *P*<sup>+</sup> value is 40.8% for *D*ITV = 75.7 Gy and *D*<sup>B</sup> = 75.6 Gy. The *P*B = 43.4% and the *P*I = 2.6% (Mavroidis et al 2007). However, if we optimize the dose level of the dose distributions in order to maximize the complication-free tumor control then for the HT, the *P*+ value becomes 68.7% for a *D*B of 86.0 Gy stemming from *P*B = 87.8% and *P*I = 19.1%. Respectively, for the MLC-based IMRT the *P*+ value becomes 72.2% for a *D*B of 85.9 Gy

Fig. 8. The DVHs of the GTV and involved lymph nodes as well as those of the organs at risk (bladder and rectum) are illustrated. The solid lines correspond to the dose distribution from Helical Tomotherapy, whereas the dashed lines correspond to the dose distribution from IMRT (Mavroidis et al. 2007) (published with permission from: Mavroidis et al. Treatment plan comparison between Helical Tomotherapy and MLC-based IMRT using radiobiological measures. Physics in Medicine and Biology, Vol.52, pp. 3829, 2007, IOP

The dose distribution in the ITV is more homogeneous in the MLC-based IMRT plan as compared to the HT, while achieving a similar sparing of the OARs. As it is shown in Fig. 9, the expected complication-free tumour control for the HT treatment plan is slightly worse than the MLC-based IMRT for the clinical prescribed doses. The reason for this is that the MLC-based IMRT irradiates more effectively the GTV and lymph nodes with better sparing of the rectum as shown in Table 2 and Fig. 9. Although the HT delivers similar mean dose to the rectum with a little larger variation as compared to the MLC-based IMRT, it shows a higher complication probability due to its higher maximum dose and the high relative

In this analysis, the clinical effectiveness of the Helical Tomotherapy and MLC-based IMRT in prostate cancer radiotherapy was evaluated using both physical and radiobiological criteria. This evaluation shows that the difference between the HT and MLC-based IMRT plans is small with the latter one being more effective over the clinically prescribed dose region. The results of this work indicate that the HT and MLC-based IMRT radiation

Publishing Ltd, http://stacks.iop.org/PMB/52/3817).

seriality value of rectum (*s* = 0.7).

having *P*B = 87.8% and *P*I = 15.5%.

modalities have almost the same potential of producing treatment plans with small integral doses to the healthy organs and fairly homogeneous doses to the ITV.

Fig. 9. The dose-response curves of the targets and organs-at-risk are plotted for the HT and MLC-based IMRT radiation modalities using the *D* on the dose axis. The vertical lines denote the clinical and optimum dose prescriptions. The solid lines correspond to the dose distribution from Helical Tomotherapy, whereas the dashed lines correspond to the dose distribution from IMRT.
