Physics Contribution
Interfraction and Intrafraction Changes in Amplitude of Breathing Motion in Stereotactic Liver Radiotherapy

Presented at the Canadian Association of Radiation Oncologists 2007 Annual Scientific Meeting, Toronto, Ontario, Canada.
https://doi.org/10.1016/j.ijrobp.2009.09.008Get rights and content

Purpose

Interfraction and intrafraction changes in amplitude of liver motion were assessed in patients with liver cancer treated with kV cone beam computed tomography (CBCT)-guided stereotactic body radiation therapy (SBRT).

Methods and Materials

A total of 314 CBCTs obtained with the patient in the treatment position immediately before and after each fraction, and 29 planning 4DCTs were evaluated in 29 patients undergoing six-fraction SBRT for unresectable liver cancer, with (n = 15) and without (n = 14) abdominal compression. Offline, the CBCTs were sorted into 10 bins, based on phase of respiration. Liver motion amplitude was measured using liver-to-liver alignment from the end-exhale and end-inhale CBCT and four-dimensional CT reconstructions. Inter- and intrafraction amplitude changes were measured from the difference between the pre-SBRT CBCTs relative to the planning four-dimensional CT, and from the pre-SBRT and post-SBRT CBCTs, respectively.

Results

Mean liver motion amplitude for all patients (range) was 1.8 (0.1–7.0), 8.0 (0.1–18.8), and 4.3 (0.1–12.1) mm in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) directions, respectively. Mean absolute inter- and intrafraction liver motion amplitude changes were 1.0 (ML), 1.7 (CC), and 1.6 (AP) mm and 1.3 (ML), 1.6 (CC), and 1.9 (AP) mm, respectively. No significant correlations were found between intrafraction amplitude change and intrafraction time (range, 4:56–25:37min:sec), and between inter- and intrafraction amplitude changes and liver motion amplitude. Intraobserver reproducibility (σ, n = 29 fractions) was 1.3 (ML), 1.4 (CC), and 1.4 (AP) mm.

Conclusions

For the majority of liver SBRT patients, the change in liver motion amplitude was minimal over the treatment course and showed no apparent relationships with the magnitude of liver motion and intrafraction time.

Introduction

Radiation therapy (RT) of liver cancers has historically played a minor role because of the low tolerance of the whole liver to radiation, and in part from the challenges in localizing the moving intrahepatic target during RT. Technological advances in the planning and delivery of RT have made it possible for tumoricidal doses of RT to be delivered to patients with unresectable tumors in the liver, while selectively sparing the surrounding healthy normal tissue.

With liver stereotactic body radiotherapy (SBRT), highly conformal, potent doses of radiation are delivered in a limited number of fractions 1, 2. Patient motion and internal organ motion needs to be considered in SBRT to deliver safe and effective treatment. Liver motion secondary to breathing is one of the largest sources of internal organ motion. The liver has been described as the “most moveable (abdominal) organ in both normal respiration and standardized breathing” (3). Strategies employed to address liver motion during RT include accounting for the motion in the planning target volume (PTV) margins (4), controlling the motion through abdominal compression (5) or breath hold techniques 6, 7, respiratory gating 8, 9, and real-time tumor tracking 10, 11.

RT planning techniques based on an assessment of an individual's tumor motion during breathing allow one to tailor treatment margins for each patient, avoiding excessively large treatment margins that may result from standardized PTV margins. Four-dimensional computed tomography (4DCT), cine magnetic resonance imaging, ultrasound, and kV fluoroscopy have been employed to measure abdominal organ motion secondary to breathing and to facilitate individualized RT plans for SBRT (4). If individualized PTV margins are to be used effectively, the motion assessed at simulation should be representative of the motion throughout the course of RT. Changes in breathing patterns of lung cancer patients 12, 13 have been observed during fractionated RT. Changes in breathing patterns during RT may lead to lower doses to tumor or higher doses to normal tissues than planned, possibly reducing local control probability or increasing toxicity. Although image-guided RT can reduce uncertainties in the mean liver position, image-guided RT cannot account for substantial changes in the amplitude of liver motion. Change in amplitude of breathing motion is more important in the context of SBRT because of the conformal plans with steep dose gradients, high total doses, and high doses per fraction delivered.

The purpose of this study was to quantify the interfraction and intrafraction changes in liver motion amplitude over the course of six-fraction liver SBRT, based on pre- and post-liver SBRT respiratory correlated kV cone beam CTs (rcCBCTs).

Section snippets

Patients

Between April 2006 to February 2008, 73 patients with unresectable metastatic or primary liver cancer and a Karnofsky performance status of at least 60 were treated as part of Institutional Research Ethics Board approved studies of six-fraction SBRT 14, 15. Among them, 44 patients were treated using a breath-hold technique and are not the focus of this paper. The remaining 29 patients were treated while free breathing, 14 with or 15 without abdominal compression and are the focus of this

Results

For the 29 who comprise the focus of this research, the 3D vector liver motion amplitude assessed on the planning 4DCTs was 10.1 (range, 2.4–19.4) mm. The average (range) liver motion amplitude from the pre-SBRT rcCBCTs was 1.8 (0.1–7.0), 8.0 (0.1–18.8), and 4.3 (0.1–12.1) mm in the ML, CC, and AP directions, respectively, and was well correlated with the 4DCT liver motion in the CC (R2 = 0.8) and AP (R2 = 0.8) directions (Fig. 2). The random (σ) and systematic (Σ) ML, CC, and AP variability in

Discussion

This study found that the liver motion amplitude changes during SBRT were small in the majority of this patient population. Eighty percent of intra- and interfraction changes were less than 3.0 mm in any direction. No significant intrafraction systematic change in breathing amplitude was observed, and there were no time trends over a 2-week course of SBRT. Mean pre-SBRT liver motion amplitude was less (0.7 mm) than planning liver motion amplitude, but this was deemed not clinically significant,

Conclusion

For the majority of study patients, liver motion amplitude was consistent over the 2-week treatment course, representing a less important source of geometric uncertainty to be considered during SBRT than changes in mean liver position relative to the bones, or “baseline shifts” in soft tissues 13, 33. Although this study was conducted offline, automated and fast measurements of tumor and liver motion using rcCBCT will be available for clinical use soon, so that confirmation of 3D liver

Acknowledgment

Thank-you to Gina Lockwood M.Math, from the department of Biostatistics, PMH, Toronto, for her thoughtful comments regarding the variability analysis, and Graham Wilson for technical support.

Jan Jakob Sonke, PhD, has a research grant funded by Elekta; Andrea Bezjak, MD, has a research grant funded by Elekta; Kristy Brock, PhD, has research grants funded by Elekta, Philips, and RaySearch, and is on the IMPAC advisory board; Laura Dawson, MD has a research grant funded by Elekta.

References (33)

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Funded in part from the National Cancer Institute of Canada, the Canadian Cancer Society and Elekta Oncology Systems.

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