Esophageal self-expandable stent material and mesh grid density are the major determining factors of external beam radiation dose perturbation: results from a phantom model

• Introduction
• Material and methods
• Results
• Radiation dose enhancement secondary to backscatter from different esophageal stents
• Esophageal stent material and mesh grid density as determinants of radiation dose enhancement
• Discussion
• References

Background: Self-expandable esophageal stents are increasingly used for palliation or as an adjunct to chemoradiation for esophageal neoplasia. The optimal esophageal stent design and material to minimize dose perturbation with external beam radiation are unknown. We sought to quantify the deviation from intended radiation dose as a function of stent material and mesh density design.

Methods: A laboratory dosimetric film model was used to quantify perturbation of intended radiation dose among 16 different esophageal stents with varying material and stent mesh density design.

Results: Radiation dose enhancement due to stent backscatter ranged from 0 % to 7.3 %, collectively representing a standard difference from the intended mean radiation dose of 1.9 (95 % confidence interval [CI] 1.5 – 2.2). This enhancement was negligible for polymer-based stents and approached 0 % for the biodegradable stents. In contrast, all metal alloy stents had significant radiation backscatter; this was largely determined by the density of mesh design and not by the type of alloy used.

Conclusions: Stent characteristics should be considered when selecting the optimal stent for treatment and palliation of malignant esophageal strictures, especially when adjuvant or neo-adjuvant radiotherapy is planned.

Introduction

The incidence of adenocarcinoma of the esophagus and gastroesophageal junction has been rising steadily over decades in the Western world, coinciding with an increase in the prevalence of obesity, gastroesophageal reflux disease, and Barrett’s esophagus [1]. Unfortunately, 50 % of patients present with inoperable disease at presentation because of distant metastasis, locally advanced disease, or prohibitive surgical risks; they therefore require chemoradiation for palliation of their disease [2] [3]. In operable disease, the paradigm has shifted from a single-modality surgical approach to a more complex multimodal algorithm. This calls for neoadjuvant chemoradiation protocols prior to definitive surgical treatment which usually occurs several weeks after completion of chemoradiotherapy [4] [5]. Restoration of the ability to eat and relief from dysphagia are, therefore, key treatment and palliation goals in the management of these patients. These goals can be achieved immediately and effectively with the use of a self-expandable metal or plastic stent (SEMS or SEPS), and more recently with expandable biodegradable stents alone, or in combination with chemoradiation protocols [6] [7] [8].

The use of SEMSs and SEPSs in the setting of malignant esophageal obstruction is associated with a number of serious adverse events including esophageal perforation, hemorrhage, and esophagorespiratory fistula that could result in a decrease in health status and quality of life [9]. The incidence of these adverse events is a function of multiple factors including the patient’s health status and co-morbidities, tumor characteristics and stage, and stent design and diameter [10]. Data on the effects of prior radiation or chemotherapy on adverse event rates after subsequent palliative esophageal stent placement are conflicting [11]. The corollary question is whether radiation scatter during radiotherapy after esophageal stent placement is significant enough to require adjustment of the radiation dose or modification to minimize serious adverse events.

Previous studies using tissue-mimicking phantom models and Monte Carlo simulations showed a significant radiation dose enhancement caused by esophageal stent placement [12] [13] [14]. However, these studies examined only a few stent types and the optimal stent material and design to minimize radiation dose perturbation in this setting could not be determined.

The aim of this study was to use dosimetric film in a laboratory model to quantify the perturbation of intended radiation dose among a wide variety of different esophageal stents, available worldwide and having varying designs and materials, to determine the optimal characteristics of stents to be used in the setting of planned radiotherapy, and to potentially minimize related adverse events.

Material and methods

The study investigated 2 stainless steel stents, 11 nitinol stents and 3 polymer-based stents ([Fig. 1]). To measure delivered radiation doses, radiochromic film (Gafchromic EBT; ISP, Wayne, New Jersey, USA) was read with a film scanner (Vidar Dosimetry Pro Advantage; Vidar, Herndon, Virginia, USA), and the results analyzed with dosimetry software (Radiological Imaging Technology 113v.5; (Colorado Springs, Colorado, USA). This film – scanner combination was found to have same-sheet uniformity of < 2 % in pre-measurement verification. All measurements were performed by an experienced radiation physicist.

The stents were each sliced so that they could be laid flat, with a layer of radiochromic EBT film on each side. The film and stents were then sandwiched between two 4-cm layers of Solid Water (CNMC, Nashville, Tennessee, USA), and exposed to a perpendicular photon beam, from one of two Varian radiotherapy treatment machines (Palo Alto, California, USA). This delivered 300 monitor units (~300 cGy) to the phantom with the stent – film sandwich, at a source-to-film distance of 100 cm in a field size of 20 × 25 cm. This arrangement provided for measurement of both forward scatter and backscatter in the same model. Both of these contributions are important in most clinical treatments that provide multiple beam directions. A dose calibration was performed on the batch of EBT film used, by comparison with a PTW Markus ion chamber. 

Three photon energies were measured for each stent; 6 megavolts (MV), 10 MV, and 18 MV. Backscatter and forward scatter effects of the film were measured based on the average central 80 % of the stent as projected on the film, normalized to regions on the same film adjacent to the stents. A control film was taken for each energy level, with the same field size and distance, to ensure that output symmetry was maintained for these measurements. Control film symmetry was within 2 % throughout the film, and < 1 % for any pair of backscatter to normal dose separations.

To compare among different stents the radiation dose enhancement due to backscatter, we averaged the quantified radiation dose enhancement at the three energy levels and the difference from the intended radiation dose was reported as a standard difference in means with 95 % confidence intervals (CI). A three-way ANOVA test was used to compare differences in radiation dose perturbation at the three energy levels used (6, 10, and 18 MV). The chi-squared test was used to compare radiation dose enhancement due to backscatter between three different stent groups, grouped by stent material and mesh grid density. All statistical analyses were done using the Comprehensive Meta-Analysis Software v2 (Biostat, Englewood, New Jersey, USA) and SAS v9.2 software (Cary, North Carolina, USA).

Results

Radiation dose enhancement secondary to backscatter from different esophageal stents

[Fig. 2] provides a visual demonstration of the existence of radiation dose enhancement in the setting of backscatter and attenuation in the setting of forward scatter with some esophageal stents, as captured by the radiochromic film. The degree of radiation dose perturbations was quantified for different esophageal stents with varying stent material and mesh grid density design and is presented in [Table 1] as percent backward and forward scatter at different radiation energy levels.

The radiation dose enhancement due to backscatter from esophageal stents ranged from 0 % to 7.3 % collectively representing a standard difference from the mean intended radiation dose of 1.9 (95 % CI 1.5 – 2.2) ([Fig. 3]). The amount of increased backscatter did not differ significantly between the three energy levels used in this study (P = 0.97). On the other hand, the average increase in dose due to forward scatter was less than 2 %, with the attenuation from the metal in the stents balancing the increase in scatter between the wires, resulting in negligible total radiation dose perturbations from forward scatter ([Table  1]).

Esophageal stent material and mesh grid density as determinants of radiation dose enhancement

[Fig. 3] shows a Forest plot of the difference from the intended radiation dose for each stent, shown as a standard difference in means with 95 % confidence interval, secondary to dose enhancement from radiation backscatter. Radiation dose enhancement was negligible for the polymer-based stents and the biodegradable SX Ella stent. No measurable backscatter, forward scatter, or attenuation was seen for the latter stent, as expected given that its density is nearly equivalent to that of water; the only dose perturbation seen was a very small region of backscatter dose increase immediately surrounding a tiny radiopaque marker attached to the stent to assist during fluoroscopically guided placement. Similarly, the PolyFlex stent had negligible dose enhancement from backscatter. However, this stent contains three reinforcing bands of radiopaque markers that circumscribe the stent at the top, middle, and bottom portions, and produced some scatter that could be readily observed and measured on the film ([Fig. 1c]).

In contrast, all metal alloy stents had significant radiation backscatter that was largely determined by the density of their mesh design and not by the type of metal alloy used. Metal stents with dense mesh designs ([Fig. 1a]) had higher radiation perturbation compared with metal stents with less dense mesh design ([Fig. 1b]) (P < 0.01).

Discussion

Despite the proven efficacy of esophageal self-expandable stents in the palliation of malignant dysphagia in the setting of unresectable esophageal neoplasia, and during the transitional neoadjuvant chemoradiation period prior to definitive surgical treatment, their use in these settings has been associated with a number of serious adverse events including esophageal perforation, fatal erosion of the aortic wall, hemorrhage, and esophagorespiratory fistula (ERF) formation [15]. These adverse events are a function of many factors including location of disease, tumor vascularity, stent characteristics, and the concomitant use of chemoradiation. Clinical data on the interaction between esophageal stents and radiotherapy and its relevance to adverse event rates are lacking. In one retrospective study a higher rate of airway adverse events (ERF, airway narrowing, or both) had occurred in patients with inoperable esophageal cancer who received radiation after stent placement (13 out of 63, 21 %) compared with before stent placement (8 out of 71, 11 %) [15].

Our bench dosimetric study corroborates the interaction between esophageal stents and radiotherapy and shows a significant dose enhancement resulting from radiation backscatter that was largely determined by the stent material (metallic versus non-metallic) and mesh grid density. Negligible scatter occurred with polymer and biodegradable stents. Amongst metal stents, stent material was not a major determinant (stainless steel vs. nitinol) but mesh grid density was. Similarly, other laboratory dosimetric studies have shown a significant degree of radiation dose enhancement in the setting of backscatter from esophageal stents; however, these studies only evaluated a limited number of esophageal stents in the attempt to determine the optimal stent characteristics to minimize this scatter [12] [13] [14]. In contrast to our study, Yan and colleagues showed greater backscatter with a polymer-based stent (PolyFlex) compared with metal stents. Their finding is confounded by overemphasis on capturing backscatter from the narrow tungsten radiopaque localization bands rather than from the stent material itself [12].

Although it is not our intention to recommend a particular stent as all currently available esophageal stents have shortcomings, the two biodegradable stents tested in our study did not produce any radiation dose perturbation, and unlike the PolyFlex stent, they have low profile radiopaque markers that minimize radiation scatter. The biodegradable SX Ella is currently only available in the European and Asian markets. It is made of polymers of polylactic or polyglycolic acid and polydioxanone. Its radial forces are maintained for 6 weeks following placement and stent disintegration occurs in about 12 weeks or sooner in the presence of low PH from acid reflux. Despite its initial marketing being targeted at benign esophageal indications, a recent study extended its use for malignant dysphagia in 17 patients, with technical and clinical success rates of 96 % and 76 %, respectively [8]. Thus, given the lack of radiation scatter observed with this stent and the adequate duration of stent wall integrity, this stent might prove useful in transitional chemoradiation periods prior to definitive treatment. Limitations of this stent, however, include the inherent difficulties in back-loading and delivering it with its current delivery system, and possible higher migration rates.

Limitations of our study include its laboratory-only nature and the fact that we sliced the stents and flattened them in the phantom model rather than maintaining their cylindrical configuration. The range of the majority of backscattered electrons, however, is just few millimeters, which is small in comparison with the radius of a deployed stent; thus, the backscatter is being produced from discrete mesh grid wires within each stent. Despite these limitations, our study provides objective evidence for a significant interaction between stent characteristics and radiation field. This interaction is yet to be confirmed in clinical settings; however, we hypothesize the amount of radiation scatter from esophageal stents in actual clinical scenarios will be even higher than that observed from the single radiation field utilized in our study, given the use of intensity-modulated radiotherapy (IMRT) that delivers multiple radiation fields from different angles.

Competing interests: None.

• References

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Corresponding author

• References

• 1 Simard EP, Ward EM, Siegel R et al. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 2012; 62: 118-128 Epub 2012 Jan 4
  CrossrefPubMedSearch in Google Scholar
• 2 Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003; 349: 2241-2252
  CrossrefPubMedSearch in Google Scholar
• 3 Blot WJ, McLaughlin JK. The changing epidemiology of esophageal cancer. Semin Oncol 1999; 26: 2-8
  PubMedSearch in Google Scholar
• 4 Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 2003; 185: 538-543
  CrossrefPubMedSearch in Google Scholar
• 5 Cunningham D, Allum WH, Stenning SP et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11-20
  CrossrefPubMedSearch in Google Scholar
• 6 Homs MY, Steyerberg EW, Eijkenboom WM et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004; 364: 1497-1504
  CrossrefPubMedSearch in Google Scholar
• 7 Bower M, Jones W, Vessels B et al. Nutritional support with endoluminal stenting during neoadjuvant therapy for esophageal malignancy. Ann Surg Oncol 2009; 16: 3161-3168
  CrossrefPubMedSearch in Google Scholar
• 8 Griffiths EA, Gregory CJ, Pursnani KG et al. The use of biodegradable (SX-ELLA) oesophageal stents to treat dysphagia due to benign and malignant oesophageal disease. Surg Endosc 2012; 26: 2367-2375 Epub 2012 Mar 7
  CrossrefPubMedSearch in Google Scholar
• 9 Homann N, Noftz MR, Klingenberg-Noftz RD et al. Delayed complications after placement of self-expanding stents in malignant esophageal obstruction: treatment strategies and survival rate. Dig Dis Sci 2008; 53: 334-340
  CrossrefPubMedSearch in Google Scholar
• 10 Sharma P, Kozarek R. Role of esophageal stents in benign and malignant diseases. Am J Gastroenterol 2010; 105: 258-273 quiz 274
  CrossrefPubMedSearch in Google Scholar
• 11 Sgourakis G, Gockel I, Radtke A et al. The use of self-expanding stents in esophageal and gastroesophageal junction cancer palliation: a meta-analysis and meta-regression analysis of outcomes. Dig Dis Sci 2010; 55: 3018-3030
  CrossrefPubMedSearch in Google Scholar
• 12 Chen YK, Schefter TE, Newman F. Esophageal cancer patients undergoing external beam radiation after placement of self-expandable metal stents: is there a risk of radiation dose enhancement?. Gastrointest Endosc 2011; 73: 1109-1114
  CrossrefPubMedSearch in Google Scholar
• 13 Atwood TF, Hsu A, Ogara MM et al. Radiotherapy dose perturbation of esophageal stents examined in an experimental model. Int J Radiat Oncol Biol Phys 2012; 82: 1659-1664
  CrossrefPubMedSearch in Google Scholar
• 14 Li XA, Chibani O, Greenwald B et al. Radiotherapy dose perturbation of metallic esophageal stents. Int J Radiat Oncol Biol Phys 2002; 54: 1276-1285
  CrossrefPubMedSearch in Google Scholar
• 15 Park JY, Shin JH, Song HY et al. Airway complications after covered stent placement for malignant esophageal stricture: special reference to radiation therapy. AJR Am J Roentgenol 2012; 198: 453-459
  CrossrefPubMedSearch in Google Scholar