The effect of breathing and set-up errors on the cumulative dose to a lung tumor

Abstract

Background and purpose: To assess the impact of both set-up errors and respiration-induced tumor motion on the cumulative dose delivered to a clinical target volume (CTV) in lung, for an irradiation based on current clinically applied field sizes.

Materials and methods: A cork phantom, having a 50 mm spherically shaped polystyrene insertion to simulate a gross tumor volume (GTV) located centrally in a lung was irradiated with two parallel opposed beams. The planned 95% isodose surface was conformed to the planning target volume (PTV) using a multi leaf collimator. The resulting margin between the CTV and the field edge was 16 mm in beam's eye view. A dose of 70 Gy was prescribed. Dose area histograms (DAHs) of the central plane of the CTV (GTV+5 mm) were determined using radiographic film for different combinations of set-up errors and respiration-induced tumor motion. The DAHs were evaluated using the population averaged tumor control probability (TCP_pop) and the equivalent uniform dose (EUD) model.

Results: Compared with dose volume histograms of the entire CTV, DAHs overestimate the impact of tumor motion on tumor control. Due to the choice of field sizes a large part of the PTV will receive a too low dose resulting in an EUD of the central plane of the CTV of 68.9 Gy for the static case. The EUD drops to 68.2, 66.1 and 51.1 Gy for systematic set-up errors of 5, 10 and 15 mm, respectively. For random set-up errors of 5, 10 and 15 mm (1 SD), the EUD decreases to 68.7, 67.4 and 64.9 Gy, respectively. For similar amplitudes of respiration-induced motion, the EUD decreases to 68.8, 68.5 and 67.7 Gy, respectively. For a clinically relevant scenario of 7.5 mm systematic set-up error, 3 mm random set-up error and 5 mm amplitude of breathing motion, the EUD is 66.7 Gy. This corresponds with a tumor control probability TCP_pop of 41.7%, compared with 50.0% for homogeneous irradiation of the CTV to 70 Gy.

Conclusion: Systematic set-up errors have a dominant effect on the cumulative dose to the CTV. The effect of breathing motion and random set-up errors is smaller. Therefore the gain of controlling breathing motion during irradiation is expected to be small and efforts should rather focus on minimizing systematic errors. For the current clinically applied field sizes and a clinically relevant combination of set-up errors and breathing motion, the EUD of the central plane of the CTV is reduced by 3.3 Gy, at maximum, relative to homogeneous irradiation of the CTV to 70 Gy, for our worst case scenario.

Introduction

The aim of radiotherapy, achieving local tumor control while sparing surrounding normal tissue, is limited by various factors. For tumors located in the thoracic cavity, the increase in the range of secondary electrons in low-density tissue with respect to soft-tissue [7], [11], [19] results in a broadening of the beam penumbra, which necessitates the use of large field margins (margin between the target volume and the field edge) in order to achieve homogeneous irradiation of the target volume. Set-up errors and respiration-induced tumor motion necessitate the use of even larger field sizes than would be required to account for the beam penumbra solely. A consequence of enlarging field sizes is an increase in dose to normal tissues like the lungs, which leads to an increased probability of complications, such as radiation pneumonitis.

Applying the nomenclature as given in ICRU report 50 [12], a geometrical structure, the planning target volume (PTV), is used as an aid for treatment planning i.e. to define beam directions, shapes and weights, and to report dose values. Treatment planning using this PTV should result in irradiation of the clinical target volume (CTV) to at least 95% of the prescribed dose during the entire course of radiotherapy. The PTV is constructed from the gross tumor volume (GTV) in two steps. Firstly, to account for the spread of sub-clinical disease, the GTV is expanded in 3-D into the CTV. Subsequently, margins are applied to this CTV to account for patient set-up errors and tumor movement, resulting in the PTV.

Ross et al. [23] analyzed multiple ultra-fast CT-scans in a group of lung cancer patients and correlated tumor motion and tumor location in the lung with the occurrence of a geometrical miss (movement of the tumor outside the beam portal). They showed that tumor movement and the chance of a geometrical miss are greatest for hilar and lower lobe lesions. Ekberg et al. [6] used fluoroscopy to determine respiration-induced motion of lung tumors for a group of patients and performed electronic portal imaging to study the reproducibility of patient set-up during a treatment course. They found systematic set-up errors of 2.0 and 3.0 mm in the transversal plane and the cranio-caudal direction, respectively. For the random set-up errors the values are 3.2 and 2.6 mm (1 SD), respectively. They combined their results into a margin of 11 mm from CTV to PTV in the transversal plane and 15 mm in the cranio caudal direction. These margins should ensure an 86% probability that the PTV encompasses the CTV throughout the treatment.

Van Herk et al. [25] developed an analytical method for selecting margins, based on all possible treatment preparation (systematic) errors, including for example the use of a non-representative CT-scan for target delineation, and treatment execution (random) errors, such as patient set-up errors and inter-fraction tumor motion. However, in case of lung tumors an extra intra-fraction tumor motion due to patient respiration is introduced, as well as a change in the resulting dose distribution due to the tumor motion, which is not (yet) incorporated in their probability-based approach.

Normal tissues like the lungs can be spared in two different ways. First of all, the margin from CTV to PTV can be reduced by using a set-up correction protocol applying multiple portal images [1], [2] or by control of tumor motion due to patient respiration during irradiation [10], [13], [14], [22], [27]. Secondly, the high dose region can be more closely conformed to the PTV using well-chosen irradiation techniques. Graham et al. [9] showed that the use of a non-coplanar beam set-up reduces the dose to normal tissues, thus allowing tumor dose escalation. However, such a procedure is achieved at the cost of an increase in treatment planning and execution time. Mohan et al. [20] showed that for a prostate treatment, beam intensity modulation, compensating for the loss of dose at the beam edges, allows the use of smaller margins and consequently allows sparing of surrounding normal tissues while improving target dose homogeneity. Lind et al. [16] showed that uncertainties in patient alignment can be taken into account by overcompensating the radiation fluence at the beam edge. In case of a lung tumor, the mean dose to the lungs, a parameter related to the incidence of radiation pneumonitis [15], can be reduced by applying such a type of intensity modulation, as shown by Brugmans et al. [3].

In a previous study [8], we showed that the choice of a field shape based on dose calculations having an inadequate inhomogeneity correction algorithm, as currently applied in much treatment planning systems, results in a too low dose to a large part of the PTV. It was, however, assumed that the treatment set-up was static. In the present study we modeled different components of tumor motion and investigated the impact of tumor motion on the cumulative 3-D dose distribution delivered to the CTV when using field sizes that are clinically applied in our institution. These field sizes are based on the equivalent pathlength inhomogeneity correction algorithm, leading to a margin of only 6 mm between PTV and field edge. A worst case scenario was used to derive an upper limit for the reduction in tumor control using these ‘too small’ field sizes in case of clinically relevant tumor motion. Furthermore, the influence of each of three components of tumor motion i.e. systematic set-up error, random set-up error and respiration-induced tumor motion, on the cumulative dose to the CTV was assessed both separately and combined. This has been done in order to identify the type of tumor motion that has the largest impact on the reduction in tumor control probability. In this study we used film measurements and an inhomogeneous phantom because our treatment planning system (TPS) does not correctly predict penumbra broadening in low-density tissue.