Brachial plexopathy after stereotactic body radiation therapy for apical lung cancer: Dosimetric analysis and preliminary clinical outcomes

Abstract

Purpose

The treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) is challenging due to the proximity of the brachial plexus and the concern for nerve damage.

Methods and materials

Between June 2009 and February 2017, a total of 75 consecutive patients underwent SBRT for T1-T3N0 non-small cell lung cancer involving the upper lobe of the lung. All patients were treated with 4-dimensional computed tomography (CT)-based image guided SBRT to a dose of 40 to 60 Gy in 3 to 5 fractions. For dosimetric analysis, only apical tumors as defined by the location of the tumor epicenter superior to the aortic arch were included. The anatomical brachial plexus was delineated using the Radiation Therapy Oncology Group atlas.

Results

Thirty-one patients with 31 apical lung tumors satisfied the anatomical criteria for inclusion. The median age was 73 years (range, 58-89). The median planning target volume was 26.5 cc (range, 8.2-81.4 cc). The median brachial plexus, brachial plexus maximum dose (Dmax), Dmax per fraction, V22 (cc, 3-4 fractions), V30 (cc, 5 fractions), and biologically effective dose 3 Gy were 15.8 Gy (range, 1.7-66.5 Gy), 3.4 Gy (range, 0.6-14.7 Gy), 0.0 cc (range, 0-0.9 cc), 0.06 cc (range, 0-2.5 cc), and 31.5 Gy (range, 3.3-133.1 Gy), respectively. At a median follow-up of 17 months, the observed incidence of brachial plexopathy was 0%.

Conclusions

There is significant variation in dose to the brachial plexus for patients treated with SBRT for apical lung tumors. Although the incidence of neuropathic symptoms in this series was zero, further attention should be focused on the clinical implications of these findings.

Introduction

Stereotactic body radiation therapy (SBRT) represents an effective treatment modality for early stage non-small cell lung cancer (NSCLC), and published series suggest that SBRT may provide similar efficacy to surgery.1,2 In comparison with conventional techniques, SBRT uses highly conformal dose distributions with ablative fraction sizes that allow for reduction of the normal tissue irradiated, intensification of the biological dose to target tissue, and a decrease in overall treatment time. Despite the low toxicity rates generally observed with SBRT, the use of these hypofractionated regimens carry a theoretical risk of normal tissue complication, particularly with respect to neural structures, where structural subunits are serially arranged and exhibit lower alpha-beta ratios, which makes them more sensitive to higher doses per fraction.3

The treatment of apical lung tumors with SBRT is especially challenging due to the proximity of the brachial plexus and the associated concern for treatment-related nerve damage. Although dose-volume tolerances of the brachial plexus have been reported for conventionally fractionated regimens for head and neck cancer, data in the setting of lung SBRT are limited.4-8 We hypothesize that despite the possibility of injury to the brachial plexus, the actual dose delivered to this critical structure is often overlooked, especially in scenarios in which target coverage to apical tumors may otherwise be compromised. The purpose of this analysis was to review of our institution’s experience with the SBRT treatment of apical lung cancers with particular focus on correlating brachial plexus dosimetric details with preliminary clinical outcomes.

Methods and materials

The medical records of 75 consecutive patients treated with SBRT for primary NSCLCinvolving the upper lobe of the lung at a tertiary-care academic medical center between June 2009 and February 2017 were reviewed. All patients underwent computed tomography (CT)–based simulation with intravenous contrast using a stereotactic body fixation device with abdominal compression to limit respiratory excursion. Four-dimensional CT was obtained, and an internal target volume (ITV) was delineated by identifying the gross tumor on maximum intensity projection image data sets considering 8 phases of the respiratory cycle. No additional margin was added for possible microscopic tumor extension. An additional margin of 5 mm circumferentially was added to the ITV to account for setup errors and to generate a planning target volume (PTV).

All tumors were treated to a dose of 40 to 60 Gy in 3 to 5 fractions with the application of heterogeneity correction. Fractions were separated by at least 40 hours, and the entire 3 to 5 fraction regimen was required to be completed within 14 days. SBRT treatment plans were generated with a combination of noncoplanar 3-dimensional conformal arcs or beams and were delivered by Novalis-TX (Brainlab AG, Munich, Germany), consisting of high-definition multileaf collimators and a 6MV-SRS (1000MU/min) beam. Treatment plans were optimized to achieve a PTV receiving 100% of the prescription dose (PTV100) of 95% or higher. Cone beam CT was used with each fraction to confirm the position of the target. Intensity modulated radiation therapy was not routinely used unless normal tissue dose constraints were exceeded with conformal beams. A Monte Carlo treatment planning algorithm was used.

Adequate target coverage was achieved when 95% of the PTV was covered by the prescription dose. High- and intermediate-dose spillages were measured by calculating the conformality index (ratio of the volume receiving 60 Gy to the PTV: ≤ 1.2) and the ratio of 50% prescription isodose volume to the PTV (R50) and by measuring the maximum dose 2 cm from the PTV in any direction (D2cm). Normal tissue structures contoured included the spinal cord, esophaguschest wall, heart, and normal lungs. The brachial plexus organ at risk (OAR) was also delineated in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines as proposed by Hall et al, although no attempt was made to limit the dose to this structure during SBRT planning.9Figure 1 illustrates a representative coronal slice of the brachial plexus depicted using the RTOG contouring atlas versus a coronal slice that was obtained from a digital reconstructed radiograph of a patient treated with SBRT in this review.

Figure 1Figure 1. Coronal slice of brachial plexus depicted using the Radiation Therapy Oncology Group contouring atlas (A) compared with a coronal slice that was obtained from a digital reconstructed radiograph of a patient who was treated with stereotactic body radiation therapy in this review. The orange structure outlines the contoured ipsilateral brachial plexus (B).

For the purposes of this analysis, only apical tumors (n = 31), defined anatomically by localizing the tumor epicenter superior to the aortic arch, were included for dosimetricevaluation. Dosimetry was subsequently reported using the following descriptive statistics: brachial plexus maximum dose (Dmax), Dmax per fraction, volume receiving 22 Gy or higher (V22, in cc, for 3-4 fractions), V30 (cc, for 5 fractions), and biologically effective dose (BED, using an alpha/beta ratio of 3) for the entire patient cohort.

The dose-volume parameters chosen for analysis were selected because they represent dose constraints on current SBRT protocols. A subset of 18 patients who were deemed to be at a higher risk due to tumor proximity (within 2 cm) to the brachial plexus were reanalyzed for the dosimetric parameters listed. Patient medical records were retrospectively reviewed to determine the incidence of brachial plexus–related symptoms, defined as the development of ipsilateral upper extremity pain, motor weakness, and/or sensory abnormalities.

Results

Table 1 outlines the characteristics of the patient population. Thirty-one patients with apical lung tumors satisfied the anatomical criteria for inclusion and comprised the primary study population. None had received previous treatment. All patients had histologically proven primary NSCLC, of which the most common histology was adenocarcinoma (52%), followed by squamous cell carcinoma (29%). The T-classification was 23 (74%) T1a, 4 (13%) T1b, 3 (10%) T2a, and 1 (3%) T3. Median patient age was 73 years (range, 58-89 years) and median PTV was 27 cc (range, 8-81 cc). Anatomically, 15 (48%) and 16 (52%) tumors were right- and left-sided, respectively. Table 2 details the characteristics of treatment. The most common prescription dose and fractionation scheme was 50 Gy in 5 fractions (n = 18). The delivered fraction size ranged from 8 to 20 Gy.

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