Physics Contribution
Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

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Purpose

To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques.

Methods and Materials

Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (Nmets) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTVmets) and of the individual metastasis planning target volume (PTVind met) were 8.7 ± 8.9 cm3 (range, 1.3-35.5 cm3) and 2.5 ± 4.5 cm3 (range, 0.19-24.7 cm3), respectively. Dose distributions in PTVmets and PTVind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and Nmets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review.

Results

Mean ± standard deviation of dose distribution characteristics derived for PTVmets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTVind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTVmets (CN = 0.737 for PTVmets ≤4.32 cm3 vs CN = 0.848 for PTVmets >4.32 cm3, P=.006), in contrast to Nmets. The achieved dose conformity to PTVmets, assessed by both CN and PITV, was in all investigated volume strata well within the best quartile of the values reported for alternative irradiation techniques.

Conclusions

HT is a well-suited technique to deliver WBRT with IB to multiple brain metastases, yielding high-quality dose distributions. A multi-institutional prospective randomized phase 2 clinical trial to exploit efficacy and safety of the treatment concept is currently under way.

Introduction

Population-based data reveal that symptomatic brain metastases develop in about 10% of cancer patients (1). Whole-brain radiation therapy (WBRT) is considered the standard treatment for patients with multiple (>3) brain metastases with a 1-year lesion control of 0% to 71% 2, 3. Stereotactic radiosurgery (RS) in addition to WBRT improves lesion control and enhances survival in patients with 1 metastasis (3). Also, for 1 to 4 metastases, WBRT combined with RS can increase intracranial lesion control (4). However, a survival benefit was not observed.

Multiple brain metastases still present a significant problem. Radiotherapeutic options include conventional fractionated WBRT, radiosurgery, or combinations of both 2, 3. Radiosurgery allows the delivery of a single high-dose fraction with highest precision, but it is restricted to few 1, 2, 3, 4 and small (<3-3.5 cm in diameter) metastases. Recently developed advanced radiation therapy techniques such as helical tomotherapy (HT) (5) enable a dose-escalated treatment compared with WBRT alone by combining WBRT with a highly conformal boost dose to the metastases in 1 treatment session 6, 7

Our group initiated a prospective phase 2 randomized clinical trial (Tomo-0701) to assess the therapeutic efficacy and safety of HT to deliver WBRT (10 × 3 Gy) with integrated boost (IB, 10 × 5 Gy) to 2 to 10 metastases as opposed to conventional WBRT. Patient recruitment started in April 2009. Here we report the treatment technique, focusing on the quantitative evaluation of the achieved dose distributions in terms of dose conformity, target coverage, and homogeneity. A systematic literature review was performed to compare the results with established RS techniques, considered the gold standard to treat single or oligo brain metastases, and with alternative approaches to deliver WBRT combined with either IB or sequential boost (SB).

Section snippets

Patient dataset

The analyzed dataset included 13 patients randomized into the HT arm of trial Tomo-0701 plus 10 additional patients who were treated with the same HT technique before the trial was opened. Included were patients with 4 to 10 metastases 3 to 40 mm in diameter and patients with 2 or 3 metastases not suited for RS.

Treatment planning

Treatment planning was based on kilovoltage computed tomography (CT) datasets with 1.5 to 2 mm slice thickness. Contouring was performed in the 3-dimensional treatment planning system

General plan characteristics

The total number of metastases in 23 patients was 81. The mean values ± standard deviation of Nmets, PTVmets, and PTVind met were 3.5 ± 1.6 (median, 3; range, 2-8), 8.7 ± 8.9 cm3 (median, 4.32 cm3; range, 1.3-35.5 cm3), and 2.5 ± 4.5 cm3 (median, 0.85 cm3; range, 0.19-24.7 cm3), respectively.

The standard parameter combination FW = 2.5 cm/pitch = 0.215/MF = 3 gave beam-on times of 10.1-14.5 minutes (mean, 12.5 ± 1 min; median, 12.7 min), which were well tolerated by all patients. The plan of the

Discussion

The quantitative evaluation of dose distribution characteristics in comparison with published values for alternative techniques has demonstrated that HT is well suited to deliver WBRT with IB to multiple brain metastases.

Conclusion

HT is a particularly suited technique to deliver WBRT with IB to patients with multiple brain metastases, yielding high-quality dose distributions that compare favorably with the majority of alternative techniques. The clinical benefit of the treatment concept is currently evaluated in a multi-institutional prospective randomized phase 2 clinical trial.

References (18)

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Supported by Grant No. STU-151/9-1 from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).

Conflict of interest: none.

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