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Measuring relief of dysphagia in locally advanced esophageal carcinoma patients submitted to high-dose-rate brachytherapy
Brachytherapy 14 (2015) 84e90
Measuring relief of dysphagia in locally advanced esophageal carcinoma patients submitted to high-dose-rate brachytherapy Rachele Grazziotin Reisner1,*, Marcio Lemberg Reisner1, Maria Aparecida Ferreira2, Arthur Accioly Rosa1, Igor Moreira Veras1, T ulio Meneses Carneiro1, Bettina Wolff1, Celia Maria Pais Viegas1, Carlos Manoel Mendonc¸a de Ara ujo1, Edson Marchiori3 1
Department of Radiation Oncology, Instituto Nacional de C^ancer, Rio de Janeiro, Brazil 2 Department of Endoscopy, Instituto Nacional de C^ancer, Rio de Janeiro, Brazil 3 Department of Radiology, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
ABSTRACT
BACKGROUND AND PURPOSE: Esophageal neoplasm has a poor prognosis, and palliative care remains an important goal of treatment. The purpose of this study was to assess the ability of highdose-rate brachytherapy (HDRB) to improve dysphagia in 115 patients treated at our institution. METHODS AND MATERIALS: Patients previously submitted to external beam radiotherapy that at least, 1 month after, presented with residual disease and persistent dysphagia, were given HDRB as palliative treatment. Patients with tumors extending to the level of cardia and those with cervical esophageal lesions were also eligible. HDRB consisted of three fractions of 500 cGy given weekly. Dysphagia was assessed using a food textureebased scale classified according to the type of food patients were able to swallow (absent, solid, pasty, or liquid). At the end of treatment, a single-category shift in dysphagia classification was scored as þ1 (e.g., liquid to pasty) or 1 (e.g., solid to pasty), and a dual-category shift was scored as þ2 (e.g., liquid to solid) or 2 (e.g., absent to pasty). RESULTS: Most patients (51.1%) had improvement of dysphagia, and 55.3% of this group experienced one-point improvement. Procedural complications included stricture (38.2%), bleeding (7%), and fistula (8.7%). In the present study, 13 patients with cervical esophageal lesions underwent HDRB without fistula formation. CONCLUSIONS: Esophageal HDRB effectively reduces dysphagia. Tumor location was not related to development of complications. Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Esophageal neoplasm; High-dose-rate brachytherapy; Dysphagia; Cervical esophagus; Palliative care
Introduction Locally advanced esophageal cancer carries a poor prognosis, and only 30e40% of patients are suitable for curative therapy (1). In such situations, palliative care to maintain optimal quality of life remains an important goal of treatment. Several palliative treatments have been used in an effort to improve dysphagia. Treatment options include surgical laser treatment (2), stent placement (3), photodynamic therapy (4), bypass surgery (5), chemotherapy Received 14 May 2014; received in revised form 15 September 2014; accepted 17 September 2014. * Corresponding author. Rua Prudente de Morais 742, apto 1401, Ipanema, Rio de Janeiro, Brazil, CEP 22420-040. Tel.: þ55-21-22474768. E-mail address: [email protected] (R. Grazziotin Reisner).
(CHT) (6e9), external beam radiation therapy (EBRT) (8e12), and brachytherapy (13e21). However, many of these procedures have significant shortcomings: laser therapy requires repeated treatment sessions because of the continuous growth of the primary tumor; metal stents are expensive, can migrate, and be blocked by food, the tumor itself, or fibrous structures; and EBRT is often too intensive for patients in poor medical condition (22, 23). High-dose-rate brachytherapy (HDRB) is an attractive palliative treatment that delivers, in a short time, a relatively high dose of irradiation to the affected area while sparing the surrounding healthy tissues. In this article, we report our experience with the use of palliative HDRB for locally advanced esophageal cancer patients, measuring the relief of dysphagia based on a food texture scale.
1538-4721/$ - see front matter Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2014.09.007
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90
Methods and materials This retrospective study included 115 patients with advanced esophageal cancer who underwent radiotherapy between August 2001 and July 2011 at the Department of Radiation Oncology of the National Cancer Institute, Rio de Janeiro, Brazil. The study protocol was approved by the institutional review board and conducted according to the ethical standards of the Declaration of Helsinki. Initial diagnostic evaluation included endoscopy, esophagography, chest X-ray, CT, and liver function testing. Diagnoses were confirmed by biopsy. Esophageal lesion location was defined according to the American Joint Committee on Cancer, Seventh Edition (24): cervical esophagus, 15e!20 cm from the incisors (upper esophageal sphincter to sternal notch); upper thoracic, 20e25 cm from the incisors (sternal notch to azygous vein); middle thoracic, 25e!30 cm from the incisors (azygous vein to inferior pulmonary vein); and lower thoracic, 30e40 cm (inferior pulmonary vein to esophagogastric junction). Patients, who were previously submitted to EBRT with or without CHT and, at least, 1 month after, presented with residual disease and persistent dysphagia, were given HDRB as palliative treatment. Patients with tumors extending to the level of the cardia and those with cervical esophageal lesions were also included. The exclusion criteria were a priori esophageal fistula or stenosis, which could not be bypassed. Twenty-two patients without post-treatment dysphagia classifications and 1 patient without pretreatment dysphagia classifications were excluded solely from the dysphagia analysis. Therefore, analyses outside the dysphagia scores involved 115 patients, whereas the dysphagia score analyses involved 92 patients.
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The procedure was performed under general anesthesia or deep sedation. Catheter insertion and fixation were performed through a flexible endoscopy tube, with guidewire dilation of the stricture if necessary to allow tube insertion. Tumor was measured by endoscopy, and proximal and distal margins were marked by a surgical clip. Frontal and lateral radiographs of the patient in the treatment position were obtained and digitalized in the BrachyVision planning system (Varian Medical Systems, Palo Alto, CA) after inactive dummy sources had been inserted into the catheters. Dwell positions and times were adjusted to optimize the dose distribution, and the catheter was connected to a Gammamed afterloading device (Varian Medical Systems). Three 500 cGy doses of radiation per fraction were prescribed at 10 mm from the source axis of the applicator (Fig. 1). The average length of lesions treated with HDRB was 6 (4e9) cm, and the mean catheter active length was 10 (8e13) cm. HDRB was performed using a total of 330 insertions with iridium-192, which has a half-life of 74.02 days and a 10-Ci rate of yield. The treated volume was determined by the extent of the disease, as measured by upper digestive endoscopy, with 2-cm proximal and distal margins based on previous published reports (17, 25e27). The mean duration of the procedure was 23 (18e28) min, including the radiography image acquisition. Endoscopies were carried out 1 month after treatment, as a routine, or more frequently, when patients’ symptoms worsened to evaluate treatment response. We classified dysphagia according to the type of food patients were able to swallow as absent (0), solid (1), pasty
Fig. 1. Isodose curves in a 52-year-old male patient with lower third esophageal cancer. He was treated to 500 cGy in a total of three fractions per week.
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(2), or liquid (3). Dysphagia was evaluated using information provided by patients or registered guardians. Postprocedural changes in dysphagia were characterized using the texture-based scale. One month after treatment, a single-category shift in dysphagia classification was scored as þ1 (e.g., liquid to pasty) or 1 (e.g., solid to pasty), and a dual-category shift was scored as þ2 (e.g., liquid to solid) or 2 (e.g., absent to pasty). Triple-category shifts were scored similarly. Statistical analysis was carried out using SPSS, version 18.0 (SPSS Inc, Chicago, IL). Prognostic variables were analyzed using the c2 or Fisher exact test to compare categorical variables and nonparametric ManneWhitney test to compare categorical and continuous variables. Survival curves and the median duration of dysphagia relief were estimated by the KaplaneMeier method and compared by log-rank test. A p-value #0.05 was considered statistically significant. Results Patient age ranged from 42 to 90 (mean, 62) years; 72% of patients were men and 41% were AfroBrazilian. The rates of smoking (77%) and alcoholism (60%) were high. Because most patients had locally advanced neoplasia or recurrent disease, treatment had a palliative intent. Epidermoid carcinoma was the predominant histological lesion type (97% of cases), and adenocarcinoma was present in 3% of cases. Moderately differentiated tumors were found with greater frequency (78%). Dysphagia was the most common symptom (90% of patients), followed by weight loss (83%), odynophagia (26%), and pain (23%). The average craniocaudal tumor length measured by endoscopy was 7.9 (1e16) cm. Most tumors were located in the middle thoracic esophagus (55, 47.8%), followed by the upper thoracic (n 5 25, 21.7%), lower thoracic (n 5 22, 19.2%), and cervical (n 5 13, 11.3%). Ninety-seven patients (84.3%) of 115 patients were submitted to exclusive EBRT with a scheme that ranged from 20 Gy in five fractions to 60 Gy in 30 fractions. The most common prescribed dose was 4500 cGy in 25 fractions, observed in 61 (63%) of 97 patients. Opposed pair technique (anteroposterioreposteroanterior) was performed in all patients, with energy varying from 1.25 to 15 MV. EBRT was combined with concurrent CHT (fluorouracil [1 g/m2] þ cisplatin [75 mg/m2]) in 15 (13%) patients. Thirty-nine patients were submitted to doses higher or equal to 50 Gy, including 24 of 97 exclusive EBRT patients and all 15 radiochemotherapy treatment patients. Sixty-one patients, as mentioned previously, were submitted to 45 Gy, and 12 patients were submitted to exclusive EBRT using a palliative hypofractionated treatment, mostly because of a poor performance status or Stage IV, which was diagnosed in 3 patients. HDRB was administered exclusively as
palliative treatment in 3 patients with locally advanced disease who could not withstand the toxicity of combined chemoradiotherapy (2.6%). Brachytherapy was always a palliative treatment, used after progression or relapse of the disease after EBRT or combined treatment and was never used as a boost. The median time from the end of the EBRT to the beginning of brachytherapy was 80 days, ranging from 40 to 690 days. All 115 patients were submitted to endoscopy at least 1 month after brachytherapy and had treatment response evaluated, although dysphagia response was not assessed in 22 patients. Average durations of followup after brachytherapy were 25 (4e208) weeks for patients who received EBRT plus HDRB and 38 (13e153) weeks for those who received treatment associated with CHT. Three exclusive brachytherapy patients were followed from 6 to 20 weeks, with an average of 12 weeks. One month after treatment, endoscopy examination showed a complete response in 22 (19.1%) patients, O50% response in 23 (20%) patients, !50% response in 19 (16.5%) patients, and disease progression in 51 (44.4%) patients. According to lesion location (cervical, upper, middle, and lower thoracic), complete response was observed in 15.4%, 21.7%, 26.4%, and 10.5% of patients, respectively; O50% response was observed in 15.4%, 23.6%, 25.8%, and 22.8% of patients; !50% response was observed in 23.1%, 9.6%, 8.3%, and 25.9% of cases; and disease progression was found in 46.1%, 45.2%, 39.5%, and 40.8% of patients, respectively. There was not a statistical relation between location and degree of response, with p 5 0.88. Although survival analysis was not the main objective of this study, the median overall survival was 23 months (Fig. 2). No patient survived for 5 years. Patients with dysphagia relief (Fig. 3) showed a 33-month median overall survival compared with 21 months observed in patients with stable or worsening of dysphagia ( p 5 0.16). Procedural complications included stricture (n 5 44, 38.2%), bleeding (n 5 8.7%), and fistula (n 5 8.7%). Esophageal dilation was performed in 29% of patients, including some patients who had received prostheses before HDRB; prostheses were deployed in 11.5% of patients. According to tumor location (cervical, upper, middle, and lower thoracic), stenosis occurred in 5 (38.5%), 11 (44%), 18 (32.7%), and 10 (45.5%) patients, respectively; bleeding occurred in 2 (15.4%), 1 (4%), 2 (3.7%), and 3 (13.6%) patients; and fistula was observed in 0 (0%), 2 (8%), 3 (5.5%), and 3 (13.6%) patients, respectively (Table 1). Tumor location and lesion size were not risk factors for the development of complications. Tumor location was not correlated to a higher risk of stricture ( p 5 0.95), fistula ( p 5 0.62), or bleeding ( p 5 0.12) (Table 1). Tumor size did not have an impact on stricture ( p 5 0.14), fistula ( p 5 0.26), or bleeding ( p 5 0.88) formation (Table 2).
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90
Fig. 2. Estimated mean overall survival of advanced esophageal cancer patients submitted to brachytherapy.
Nine patients were older than 80 years, and all of them, with one exception, presented stenosis. Fistula occurred in 1 patient aged 90 years.
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The most common pretreatment degree of dysphagia was characterized by the difficulty in swallowing solid food (n 5 56; 49.1%), followed by liquids (n 5 27; 23.6%), pasty food (n 5 23; 20.2%), and the absence of dysphagia (n 5 8; 7%). This was assessed in a total of 114 patients because 1 patient did not have a preevaluation dysphagia score. Post-treatment dysphagia evaluation was missing in 22 patients, giving a total of 92 patients with dysphagia score analyzed. Among patients with initial ‘‘liquid’’ dysphagia classifications, post-treatment evaluation indicated stability in six cases and improvement in 19 cases (þ1, n 5 6; þ2, n 5 9; and þ3, n 5 4). Among patients with initial ‘‘pasty food’’ dysphagia classifications, post-treatment evaluation indicated worsening (1) in two cases, stability in two cases, and improvement in 16 cases (þ1, n 5 8 and þ2, n 5 8). Among those with initial ‘‘solid food’’ dysphagia classifications, 16 patients showed worsening post-treatment (1, n 5 10 and 2, n 5 6), 15 patients remained stable, and 12 achieved improvement. Among those without dysphagia, 1 patient showed worsening post-treatment (1, n 5 1), and 3 patients remained stable. Overall, dysphagia worsened in 19 patients (20.6%), remained unchanged in 26 patients (28.3%), and improved in 47 patients (51.1%). Among patients with dysphagia improvement, þ1, þ2, and þ3 point improvements were observed in 55.3%, 36.2%, and 8.5%, respectively (Table 3). In a 4-year followup analysis of the 51.1% patients who had improvement of dysphagia, the median duration of the dysphagia relief was 5.3 months (159 days), with a large range from 1 month to 35 months.
Discussion
Fig. 3. KaplaneMeier curves comparing overall survival of patients stratified by dysphagia. Legend: green linedpatients with dysphagia relief and blue linedpatients without dysphagia relief. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)
According to Radiation Therapy Oncology Group 8501 (25), one of the major studies involving chemoradiation in advanced esophageal cancer, only 26% of patients are to be expected to be alive in 5 years. Thus, the maintenance or improvement of quality of life, especially with regard to dysphagia, is an important aspect of treatment in esophageal cancer patients. Brewster et al. (16) suggested that the improvement of dysphagia could be considered a prognostic factor. Sur et al. (17) demonstrated that the dysphagia-free survival rate was associated with an average survival gain of 16.5 months in patients who underwent HDRB, compared with 9 months in patients who did not receive this therapy. This study showed a higher median overall survival of the subgroup of patients with dysphagia relief (33 months) opposed to the group without improvement in dysphagia (21 months) although it did not reach statistical significance ( p 5 0.16). Skowronek et al. (19) also showed a significant correlation between dysphagia and survival, with higher survival rates observed in patients with Grade II (semisolid food) dysphagia than in those with Grades III (liquids) and IV (total) dysphagia.
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Table 1 Location complications Stenosis
Fistula
Yes
No
Bleeding
Yes
No
Yes
No
Location
n
%
n
%
n
%
n
%
n
%
n
%
Cervical Upper thoracic Middle thoracic Lower thoracic Total p-Value
5 11 18 10 44 0.952
38.5 44.0 32.7 45.5 38.2
8 14 37 12 71
61.5 56 67.3 54.5 61.8
0 2 3 3 8 0.628
0 8 5.5 13.6 7
13 23 52 19 107
100 92 94.5 86.4 93.0
2 1 2 3 8 0.121
15.4 4.0 3.7 13.6 7.0
11 24 53 19 107
84.6 96.0 96.3 86.4 93.0
n 5 number; % 5 percentage.
Although two studies published by Okawa et al. (20) and Iwasa et al. (21) showed that some subgroup patients could also benefit from the addition of brachytherapy to their therapeutic regimens, in our institution, HDRB was always used as a palliative treatment, based on the results of a Phase II Radiation Therapy Oncology Group 9207. This article, published by Gaspar et al. (26), showed a lifethreatening toxicity and treatment-related death occurring in 24% and 10% of cases, respectively, without any evidence of benefit of brachytherapy as a boost, performed 2 weeks after completing EBRT. The median duration of the dysphagia relief found in this study (159 days) was longer compared with the previous referred data, published by Homs et al. (27), which showed 115 survival days without dysphagia. This possibly may be explained by a higher fractionation scheme of three fractions of 500 cGy each compared with a single dose of 1200 cGy in the study by Homs et al. (27). The study published by Harvey et al. (28) also suggested better results with a three-fraction scheme. Patients submitted to single fraction presented a lower mean dysphagia relief (135 days) compared with our study. However, patients receiving a three-fraction scheme presented a similar mean dysphagia relief (153 days). Sur et al. (17) in a second randomized trial, comparing 18 Gy in three fractions and 16 Gy in two fractions, showed even a longer mean dysphagia relief and a dysphagia-free survival of 7.1 months. These results could be explained by a higher number of patients (88.4% of 236) classified with pretreatment solid dysphagia compared with 49.1% in this study. Because most lesions observed in our study were large (mean length of 7.93 cm), all patients were submitted to
a three-fraction scheme. Although Rowland and Pagliero (29) as well as Jager et al. (18) reported favorable results with a single-dose regimen, this scheme was avoided because of a potential lower rate of dysphagia relief and a higher risk of complications. This was based on larger sample studies than those reported previously, published by Brewster et al. (16) and Homs et al. (27), which showed lower rates (57% and 51%, respectively) of dysphagia response using a single dose. A recent report (30) demonstrated minimal toxicity with a three-fraction scheme and concluded that a mucosal dose of !1200 cGy could significantly decrease ulceration, stricture, and fistula formation. Few published studies have evaluated the use of esophageal HDRB in advanced disease in samples of more than 90 patients (16, 17, 31). For this reason, we report our results in relation to dysphagia relief and response and complication rates, as our patients represent most patients with esophageal cancer worldwide in terms of poor performance status, malnourishment, extremely advanced disease, and treatment within the public health system of a developing country. These factors likely explain our inferior outcomes of dysphagia relief in comparison with those of previous studies. Studies with small samples have reported improvement of dysphagia in 65e90% of patients (28, 29, 32), and those with larger samples have reported 51e67% improvement (16, 18, 31). All these studies were conducted in developed countries, such as England, the United States, and the Netherlands. Studies in developing countries, such as South Africa (33), have obtained results similar to those of this study, with 1year dysphagia-free survival rates of 28.9% in the entire study population (10.8% in patients receiving 1200 cGy in two fractions, 25.43% in those receiving 1600 cGy in two
Table 2 Stricture size Yes Complication Tumor Size n Stricture Fistula Bleeding
No Mean Median Minimum Maximum size (cm) size (cm) SD (cm) (cm) (cm) n
44 4.30 8 3.66 8 4.88
5.00 4.00 6.00
2.98 3.46 3.31
0 0 0
n 5 number; cm 5 centimeters; SD 5 standard deviation.
9 9 9
Mean Median Minimum Maximum size (cm) size (cm) SD (cm) (cm) (cm) p-Value
71 5.39 107 5.07 107 4.98
6.00 6.00 6.00
3.96 3.64 3.68
0 0 0
16 16 16
0.14 0.27 0.88
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90 Table 3 Dysphagia response analysis Dysphagia score Dysphagia Dysphagia post-treatment post-treatment pretreatment Absent Liquid. NR Pasty Solid Total 1
2 0
1
2
3 NR
Absent Pasty Solid Total Solid Total Absent Liquid Pasty Solid Total Liquid Pasty Solid Total Liquid Pasty Total Liquid Total Absent Liquid NR Pasty Solid Total
1 2 10 10
2 6 6
1
3 6 2 3
6
2 6
15 16 8
12 12
6
8 8 4 4
8 9 9
4 2 1 3 13 22
1
1 2 10 13 6 6 3 6 2 15 26 6 8 12 26 9 8 17 4 4 4 1 1 3 13 23
NR 5 nonregistered.
fractions, and 38.95% in patients receiving 1800 cGy in three fractions). Sharma et al. (1) reported their experience in a large hospital in Mumbai, India, showing improved swallowing function in 43% of untreated patients and 28.5% in patients with recurrent disease, and the maintenance of pretreatment status in 41% of patients. According to the point scale created to measure the relief of dysphagia, most patients presented one-point improvement, showing a real benefit from HDRB. Our scale was similar to the scale used by Amdal et al. (34), which evaluated the benefit of brachytherapy with or without primary stent placement. Our results were quite similar to that study, with both presenting similar mean length tumor of 7 cm and most patients with one-point improvement of dysphagia. Homs et al. (35) also elaborated a dysphagia scale with different grades, varying from 0 (ability to eat a normal diet) to 4 (complete dysphagia), showing an improvement of two to three points in esophageal cancer patients treated in the Netherlands. As mentioned previously, these better results were possibly explained by a shorter mean length (6.8 cm) when compared with the mean length (7.9 cm) of this study. Although the high number of advanced lesions, complication rates observed in the present study, particularly those of bleeding and fistula (7%), were consistent with previous reports (17, 19, 27).
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It is important to notice that the most common complications (bleeding, fistula, and stricture) were not related to the location of the treatment, which could give basis to the confident use of HDRB in upper esophageal lesions. HDRB is contraindicated in cervical esophageal lesions, mainly because of the risk of fistula formation (26). In the present study, 13 patients with cervical esophageal lesions underwent HDRB with no fistula formation (Table 1). This result corroborates those obtained in a series of 91 patients, including 6 patients with cervical esophageal tumors, which showed no correlation between complication rates and tumor location; the authors concluded that fistula rates were tumor related, rather than treatment related (19). Moreover, as mentioned previously, location was not related to degree of response, giving equal chances of satisfactory response in cervical esophagus compared with other locations. It is important to notice that this study has some limitations, especially because of its retrospective nature. In addition, in some patients, it was difficult to determine if HDRB was solely the cause of stenosis, or it was also related to the tumor itself.
Conclusion In conclusion, esophageal HDRB effectively reduces dysphagia and provides rapid palliation with lower complication rates. Patients with cervical esophageal cancer can undergo palliative HDRB with no additional risk of complication.
Acknowledgments We thank Simone Reisner, Isabella Small, and Thalita da Matta de Castro for their support. References [1] Sharma V, Mahantshetty U, Dinshaw KA, et al. Palliation of advanced/recurrent esophageal carcinoma with high-dose-rate brachytherapy. [Review]. Int J Radiat Oncol Biol Phys 2002;52:310e315. [2] Yano T, Muto M, Minashi K, et al. Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: A phase II study. Int J Cancer 2012;131:1228e1234. [3] Didden P, Spaander MC, Kuipers EJ, et al. Safety of stent placement in recurrent or persistent esophageal cancer after definitive chemoradiotherapy: A case series. Gastrointest Endosc 2012;76:426e430. [4] Lindenmann J, Matzi V, Neuboeck N, et al. Individualized, multimodal palliative treatment of inoperable esophageal cancer: Clinical impact of photodynamic therapy resulting in prolonged survival. Lasers Surg Med 2012;44:189e198. [5] Aoki T, Osaka Y, Takagi Y. Comparative study of self-expandable metallic stent and bypass surgery for inoperable esophageal cancer. Dis Esophagus 2001;14:208e211. [6] Adenis A, Penel N, Horn S, et al. Palliative chemotherapy does not improve survival in metastatic esophageal cancer. Oncology 2010; 79:46e54.
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Therapeutic Radiology and Oncology (JASTRO) Study Group. Int J Radiat Oncol Biol Phys 1999;45:623e628. Iwasa M, Ohmori Y, Iwasa Y, et al. Effect of multidisciplinary treatment with high dose rate intraluminal brachytherapy on survival in patients with unresectable esophageal cancer. Dig Surg 1998;15: 227e235. Knyrim K, Wagner HJ, Bethge N, et al. A controlled trial of an expansile metal stent for palliation of esophageal obstruction due to inoperable cancer. N Engl J Med 1993;329:1302e1307. Qiu G, Tao Y, Du X, et al. The impact of prior radiotherapy on fatal complications after self-expandable metallic stents (SEMS) for malignant dysphagia due to esophageal carcinoma. Dis Esophagus 2013;26:175e178. Edge SB, Byrd DR, Carducci MA, et al, editors. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2009. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593e1598. Gaspar LE, Nag S, Herskovic A, et al. American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys 1997;38: 127e132. 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;364:1497e1504. Harvey JC, Fleischman EH, Bellotti JE, et al. Intracavitary radiation in the treatment of advanced esophageal carcinoma: A comparison of high dose rate vs. low dose rate brachytherapy. J Surg Oncol 1993;52: 101e104. Rowland CG, Pagliero KM. Intracavitary irradiation in palliation of carcinoma of oesophagus and cardia. Lancet 1985;2:981e983. Folkert MR, Cohen GN, Wu AJ, et al. Endoluminal high-dose-rate brachytherapy for early stage and recurrent esophageal cancer in medically inoperable patients. Brachytherapy 2013;12:463e470. Homs MY, Steyerberg EW, Eijkenboom WM, et al. Dutch SIREC Study Group. Predictors of outcome of single-dose brachytherapy for the palliation of dysphagia from esophageal cancer. Brachytherapy 2006;5:41e48. Leung JT, Kuan R. Brachytherapy in oesophageal carcinoma. Australas Radiol 1995;39:375e378. Sur RK, Donde B, Levin VC, et al. Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer. Int J Radiat Oncol Biol Phys 1998;40:447e453. Amdal CD, Jacobsen AB, Sandstad B, et al. Palliative brachytherapy with or without primary stent placement in patients with oesophageal cancer, a randomised phase III trial. Radiother Oncol 2013;107: 428e433. Homs MY, Eijkenboom WM, Coen VL, et al. High dose rate brachytherapy for the palliation of malignant dysphagia. Radiother Oncol 2003;66:327e332.
Measuring relief of dysphagia in locally advanced esophageal carcinoma patients submitted to high-dose-rate brachytherapy Rachele Grazziotin Reisner1,*, Marcio Lemberg Reisner1, Maria Aparecida Ferreira2, Arthur Accioly Rosa1, Igor Moreira Veras1, T ulio Meneses Carneiro1, Bettina Wolff1, Celia Maria Pais Viegas1, Carlos Manoel Mendonc¸a de Ara ujo1, Edson Marchiori3 1
Department of Radiation Oncology, Instituto Nacional de C^ancer, Rio de Janeiro, Brazil 2 Department of Endoscopy, Instituto Nacional de C^ancer, Rio de Janeiro, Brazil 3 Department of Radiology, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
ABSTRACT
BACKGROUND AND PURPOSE: Esophageal neoplasm has a poor prognosis, and palliative care remains an important goal of treatment. The purpose of this study was to assess the ability of highdose-rate brachytherapy (HDRB) to improve dysphagia in 115 patients treated at our institution. METHODS AND MATERIALS: Patients previously submitted to external beam radiotherapy that at least, 1 month after, presented with residual disease and persistent dysphagia, were given HDRB as palliative treatment. Patients with tumors extending to the level of cardia and those with cervical esophageal lesions were also eligible. HDRB consisted of three fractions of 500 cGy given weekly. Dysphagia was assessed using a food textureebased scale classified according to the type of food patients were able to swallow (absent, solid, pasty, or liquid). At the end of treatment, a single-category shift in dysphagia classification was scored as þ1 (e.g., liquid to pasty) or 1 (e.g., solid to pasty), and a dual-category shift was scored as þ2 (e.g., liquid to solid) or 2 (e.g., absent to pasty). RESULTS: Most patients (51.1%) had improvement of dysphagia, and 55.3% of this group experienced one-point improvement. Procedural complications included stricture (38.2%), bleeding (7%), and fistula (8.7%). In the present study, 13 patients with cervical esophageal lesions underwent HDRB without fistula formation. CONCLUSIONS: Esophageal HDRB effectively reduces dysphagia. Tumor location was not related to development of complications. Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Esophageal neoplasm; High-dose-rate brachytherapy; Dysphagia; Cervical esophagus; Palliative care
Introduction Locally advanced esophageal cancer carries a poor prognosis, and only 30e40% of patients are suitable for curative therapy (1). In such situations, palliative care to maintain optimal quality of life remains an important goal of treatment. Several palliative treatments have been used in an effort to improve dysphagia. Treatment options include surgical laser treatment (2), stent placement (3), photodynamic therapy (4), bypass surgery (5), chemotherapy Received 14 May 2014; received in revised form 15 September 2014; accepted 17 September 2014. * Corresponding author. Rua Prudente de Morais 742, apto 1401, Ipanema, Rio de Janeiro, Brazil, CEP 22420-040. Tel.: þ55-21-22474768. E-mail address: [email protected] (R. Grazziotin Reisner).
(CHT) (6e9), external beam radiation therapy (EBRT) (8e12), and brachytherapy (13e21). However, many of these procedures have significant shortcomings: laser therapy requires repeated treatment sessions because of the continuous growth of the primary tumor; metal stents are expensive, can migrate, and be blocked by food, the tumor itself, or fibrous structures; and EBRT is often too intensive for patients in poor medical condition (22, 23). High-dose-rate brachytherapy (HDRB) is an attractive palliative treatment that delivers, in a short time, a relatively high dose of irradiation to the affected area while sparing the surrounding healthy tissues. In this article, we report our experience with the use of palliative HDRB for locally advanced esophageal cancer patients, measuring the relief of dysphagia based on a food texture scale.
1538-4721/$ - see front matter Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2014.09.007
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90
Methods and materials This retrospective study included 115 patients with advanced esophageal cancer who underwent radiotherapy between August 2001 and July 2011 at the Department of Radiation Oncology of the National Cancer Institute, Rio de Janeiro, Brazil. The study protocol was approved by the institutional review board and conducted according to the ethical standards of the Declaration of Helsinki. Initial diagnostic evaluation included endoscopy, esophagography, chest X-ray, CT, and liver function testing. Diagnoses were confirmed by biopsy. Esophageal lesion location was defined according to the American Joint Committee on Cancer, Seventh Edition (24): cervical esophagus, 15e!20 cm from the incisors (upper esophageal sphincter to sternal notch); upper thoracic, 20e25 cm from the incisors (sternal notch to azygous vein); middle thoracic, 25e!30 cm from the incisors (azygous vein to inferior pulmonary vein); and lower thoracic, 30e40 cm (inferior pulmonary vein to esophagogastric junction). Patients, who were previously submitted to EBRT with or without CHT and, at least, 1 month after, presented with residual disease and persistent dysphagia, were given HDRB as palliative treatment. Patients with tumors extending to the level of the cardia and those with cervical esophageal lesions were also included. The exclusion criteria were a priori esophageal fistula or stenosis, which could not be bypassed. Twenty-two patients without post-treatment dysphagia classifications and 1 patient without pretreatment dysphagia classifications were excluded solely from the dysphagia analysis. Therefore, analyses outside the dysphagia scores involved 115 patients, whereas the dysphagia score analyses involved 92 patients.
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The procedure was performed under general anesthesia or deep sedation. Catheter insertion and fixation were performed through a flexible endoscopy tube, with guidewire dilation of the stricture if necessary to allow tube insertion. Tumor was measured by endoscopy, and proximal and distal margins were marked by a surgical clip. Frontal and lateral radiographs of the patient in the treatment position were obtained and digitalized in the BrachyVision planning system (Varian Medical Systems, Palo Alto, CA) after inactive dummy sources had been inserted into the catheters. Dwell positions and times were adjusted to optimize the dose distribution, and the catheter was connected to a Gammamed afterloading device (Varian Medical Systems). Three 500 cGy doses of radiation per fraction were prescribed at 10 mm from the source axis of the applicator (Fig. 1). The average length of lesions treated with HDRB was 6 (4e9) cm, and the mean catheter active length was 10 (8e13) cm. HDRB was performed using a total of 330 insertions with iridium-192, which has a half-life of 74.02 days and a 10-Ci rate of yield. The treated volume was determined by the extent of the disease, as measured by upper digestive endoscopy, with 2-cm proximal and distal margins based on previous published reports (17, 25e27). The mean duration of the procedure was 23 (18e28) min, including the radiography image acquisition. Endoscopies were carried out 1 month after treatment, as a routine, or more frequently, when patients’ symptoms worsened to evaluate treatment response. We classified dysphagia according to the type of food patients were able to swallow as absent (0), solid (1), pasty
Fig. 1. Isodose curves in a 52-year-old male patient with lower third esophageal cancer. He was treated to 500 cGy in a total of three fractions per week.
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(2), or liquid (3). Dysphagia was evaluated using information provided by patients or registered guardians. Postprocedural changes in dysphagia were characterized using the texture-based scale. One month after treatment, a single-category shift in dysphagia classification was scored as þ1 (e.g., liquid to pasty) or 1 (e.g., solid to pasty), and a dual-category shift was scored as þ2 (e.g., liquid to solid) or 2 (e.g., absent to pasty). Triple-category shifts were scored similarly. Statistical analysis was carried out using SPSS, version 18.0 (SPSS Inc, Chicago, IL). Prognostic variables were analyzed using the c2 or Fisher exact test to compare categorical variables and nonparametric ManneWhitney test to compare categorical and continuous variables. Survival curves and the median duration of dysphagia relief were estimated by the KaplaneMeier method and compared by log-rank test. A p-value #0.05 was considered statistically significant. Results Patient age ranged from 42 to 90 (mean, 62) years; 72% of patients were men and 41% were AfroBrazilian. The rates of smoking (77%) and alcoholism (60%) were high. Because most patients had locally advanced neoplasia or recurrent disease, treatment had a palliative intent. Epidermoid carcinoma was the predominant histological lesion type (97% of cases), and adenocarcinoma was present in 3% of cases. Moderately differentiated tumors were found with greater frequency (78%). Dysphagia was the most common symptom (90% of patients), followed by weight loss (83%), odynophagia (26%), and pain (23%). The average craniocaudal tumor length measured by endoscopy was 7.9 (1e16) cm. Most tumors were located in the middle thoracic esophagus (55, 47.8%), followed by the upper thoracic (n 5 25, 21.7%), lower thoracic (n 5 22, 19.2%), and cervical (n 5 13, 11.3%). Ninety-seven patients (84.3%) of 115 patients were submitted to exclusive EBRT with a scheme that ranged from 20 Gy in five fractions to 60 Gy in 30 fractions. The most common prescribed dose was 4500 cGy in 25 fractions, observed in 61 (63%) of 97 patients. Opposed pair technique (anteroposterioreposteroanterior) was performed in all patients, with energy varying from 1.25 to 15 MV. EBRT was combined with concurrent CHT (fluorouracil [1 g/m2] þ cisplatin [75 mg/m2]) in 15 (13%) patients. Thirty-nine patients were submitted to doses higher or equal to 50 Gy, including 24 of 97 exclusive EBRT patients and all 15 radiochemotherapy treatment patients. Sixty-one patients, as mentioned previously, were submitted to 45 Gy, and 12 patients were submitted to exclusive EBRT using a palliative hypofractionated treatment, mostly because of a poor performance status or Stage IV, which was diagnosed in 3 patients. HDRB was administered exclusively as
palliative treatment in 3 patients with locally advanced disease who could not withstand the toxicity of combined chemoradiotherapy (2.6%). Brachytherapy was always a palliative treatment, used after progression or relapse of the disease after EBRT or combined treatment and was never used as a boost. The median time from the end of the EBRT to the beginning of brachytherapy was 80 days, ranging from 40 to 690 days. All 115 patients were submitted to endoscopy at least 1 month after brachytherapy and had treatment response evaluated, although dysphagia response was not assessed in 22 patients. Average durations of followup after brachytherapy were 25 (4e208) weeks for patients who received EBRT plus HDRB and 38 (13e153) weeks for those who received treatment associated with CHT. Three exclusive brachytherapy patients were followed from 6 to 20 weeks, with an average of 12 weeks. One month after treatment, endoscopy examination showed a complete response in 22 (19.1%) patients, O50% response in 23 (20%) patients, !50% response in 19 (16.5%) patients, and disease progression in 51 (44.4%) patients. According to lesion location (cervical, upper, middle, and lower thoracic), complete response was observed in 15.4%, 21.7%, 26.4%, and 10.5% of patients, respectively; O50% response was observed in 15.4%, 23.6%, 25.8%, and 22.8% of patients; !50% response was observed in 23.1%, 9.6%, 8.3%, and 25.9% of cases; and disease progression was found in 46.1%, 45.2%, 39.5%, and 40.8% of patients, respectively. There was not a statistical relation between location and degree of response, with p 5 0.88. Although survival analysis was not the main objective of this study, the median overall survival was 23 months (Fig. 2). No patient survived for 5 years. Patients with dysphagia relief (Fig. 3) showed a 33-month median overall survival compared with 21 months observed in patients with stable or worsening of dysphagia ( p 5 0.16). Procedural complications included stricture (n 5 44, 38.2%), bleeding (n 5 8.7%), and fistula (n 5 8.7%). Esophageal dilation was performed in 29% of patients, including some patients who had received prostheses before HDRB; prostheses were deployed in 11.5% of patients. According to tumor location (cervical, upper, middle, and lower thoracic), stenosis occurred in 5 (38.5%), 11 (44%), 18 (32.7%), and 10 (45.5%) patients, respectively; bleeding occurred in 2 (15.4%), 1 (4%), 2 (3.7%), and 3 (13.6%) patients; and fistula was observed in 0 (0%), 2 (8%), 3 (5.5%), and 3 (13.6%) patients, respectively (Table 1). Tumor location and lesion size were not risk factors for the development of complications. Tumor location was not correlated to a higher risk of stricture ( p 5 0.95), fistula ( p 5 0.62), or bleeding ( p 5 0.12) (Table 1). Tumor size did not have an impact on stricture ( p 5 0.14), fistula ( p 5 0.26), or bleeding ( p 5 0.88) formation (Table 2).
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90
Fig. 2. Estimated mean overall survival of advanced esophageal cancer patients submitted to brachytherapy.
Nine patients were older than 80 years, and all of them, with one exception, presented stenosis. Fistula occurred in 1 patient aged 90 years.
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The most common pretreatment degree of dysphagia was characterized by the difficulty in swallowing solid food (n 5 56; 49.1%), followed by liquids (n 5 27; 23.6%), pasty food (n 5 23; 20.2%), and the absence of dysphagia (n 5 8; 7%). This was assessed in a total of 114 patients because 1 patient did not have a preevaluation dysphagia score. Post-treatment dysphagia evaluation was missing in 22 patients, giving a total of 92 patients with dysphagia score analyzed. Among patients with initial ‘‘liquid’’ dysphagia classifications, post-treatment evaluation indicated stability in six cases and improvement in 19 cases (þ1, n 5 6; þ2, n 5 9; and þ3, n 5 4). Among patients with initial ‘‘pasty food’’ dysphagia classifications, post-treatment evaluation indicated worsening (1) in two cases, stability in two cases, and improvement in 16 cases (þ1, n 5 8 and þ2, n 5 8). Among those with initial ‘‘solid food’’ dysphagia classifications, 16 patients showed worsening post-treatment (1, n 5 10 and 2, n 5 6), 15 patients remained stable, and 12 achieved improvement. Among those without dysphagia, 1 patient showed worsening post-treatment (1, n 5 1), and 3 patients remained stable. Overall, dysphagia worsened in 19 patients (20.6%), remained unchanged in 26 patients (28.3%), and improved in 47 patients (51.1%). Among patients with dysphagia improvement, þ1, þ2, and þ3 point improvements were observed in 55.3%, 36.2%, and 8.5%, respectively (Table 3). In a 4-year followup analysis of the 51.1% patients who had improvement of dysphagia, the median duration of the dysphagia relief was 5.3 months (159 days), with a large range from 1 month to 35 months.
Discussion
Fig. 3. KaplaneMeier curves comparing overall survival of patients stratified by dysphagia. Legend: green linedpatients with dysphagia relief and blue linedpatients without dysphagia relief. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)
According to Radiation Therapy Oncology Group 8501 (25), one of the major studies involving chemoradiation in advanced esophageal cancer, only 26% of patients are to be expected to be alive in 5 years. Thus, the maintenance or improvement of quality of life, especially with regard to dysphagia, is an important aspect of treatment in esophageal cancer patients. Brewster et al. (16) suggested that the improvement of dysphagia could be considered a prognostic factor. Sur et al. (17) demonstrated that the dysphagia-free survival rate was associated with an average survival gain of 16.5 months in patients who underwent HDRB, compared with 9 months in patients who did not receive this therapy. This study showed a higher median overall survival of the subgroup of patients with dysphagia relief (33 months) opposed to the group without improvement in dysphagia (21 months) although it did not reach statistical significance ( p 5 0.16). Skowronek et al. (19) also showed a significant correlation between dysphagia and survival, with higher survival rates observed in patients with Grade II (semisolid food) dysphagia than in those with Grades III (liquids) and IV (total) dysphagia.
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Table 1 Location complications Stenosis
Fistula
Yes
No
Bleeding
Yes
No
Yes
No
Location
n
%
n
%
n
%
n
%
n
%
n
%
Cervical Upper thoracic Middle thoracic Lower thoracic Total p-Value
5 11 18 10 44 0.952
38.5 44.0 32.7 45.5 38.2
8 14 37 12 71
61.5 56 67.3 54.5 61.8
0 2 3 3 8 0.628
0 8 5.5 13.6 7
13 23 52 19 107
100 92 94.5 86.4 93.0
2 1 2 3 8 0.121
15.4 4.0 3.7 13.6 7.0
11 24 53 19 107
84.6 96.0 96.3 86.4 93.0
n 5 number; % 5 percentage.
Although two studies published by Okawa et al. (20) and Iwasa et al. (21) showed that some subgroup patients could also benefit from the addition of brachytherapy to their therapeutic regimens, in our institution, HDRB was always used as a palliative treatment, based on the results of a Phase II Radiation Therapy Oncology Group 9207. This article, published by Gaspar et al. (26), showed a lifethreatening toxicity and treatment-related death occurring in 24% and 10% of cases, respectively, without any evidence of benefit of brachytherapy as a boost, performed 2 weeks after completing EBRT. The median duration of the dysphagia relief found in this study (159 days) was longer compared with the previous referred data, published by Homs et al. (27), which showed 115 survival days without dysphagia. This possibly may be explained by a higher fractionation scheme of three fractions of 500 cGy each compared with a single dose of 1200 cGy in the study by Homs et al. (27). The study published by Harvey et al. (28) also suggested better results with a three-fraction scheme. Patients submitted to single fraction presented a lower mean dysphagia relief (135 days) compared with our study. However, patients receiving a three-fraction scheme presented a similar mean dysphagia relief (153 days). Sur et al. (17) in a second randomized trial, comparing 18 Gy in three fractions and 16 Gy in two fractions, showed even a longer mean dysphagia relief and a dysphagia-free survival of 7.1 months. These results could be explained by a higher number of patients (88.4% of 236) classified with pretreatment solid dysphagia compared with 49.1% in this study. Because most lesions observed in our study were large (mean length of 7.93 cm), all patients were submitted to
a three-fraction scheme. Although Rowland and Pagliero (29) as well as Jager et al. (18) reported favorable results with a single-dose regimen, this scheme was avoided because of a potential lower rate of dysphagia relief and a higher risk of complications. This was based on larger sample studies than those reported previously, published by Brewster et al. (16) and Homs et al. (27), which showed lower rates (57% and 51%, respectively) of dysphagia response using a single dose. A recent report (30) demonstrated minimal toxicity with a three-fraction scheme and concluded that a mucosal dose of !1200 cGy could significantly decrease ulceration, stricture, and fistula formation. Few published studies have evaluated the use of esophageal HDRB in advanced disease in samples of more than 90 patients (16, 17, 31). For this reason, we report our results in relation to dysphagia relief and response and complication rates, as our patients represent most patients with esophageal cancer worldwide in terms of poor performance status, malnourishment, extremely advanced disease, and treatment within the public health system of a developing country. These factors likely explain our inferior outcomes of dysphagia relief in comparison with those of previous studies. Studies with small samples have reported improvement of dysphagia in 65e90% of patients (28, 29, 32), and those with larger samples have reported 51e67% improvement (16, 18, 31). All these studies were conducted in developed countries, such as England, the United States, and the Netherlands. Studies in developing countries, such as South Africa (33), have obtained results similar to those of this study, with 1year dysphagia-free survival rates of 28.9% in the entire study population (10.8% in patients receiving 1200 cGy in two fractions, 25.43% in those receiving 1600 cGy in two
Table 2 Stricture size Yes Complication Tumor Size n Stricture Fistula Bleeding
No Mean Median Minimum Maximum size (cm) size (cm) SD (cm) (cm) (cm) n
44 4.30 8 3.66 8 4.88
5.00 4.00 6.00
2.98 3.46 3.31
0 0 0
n 5 number; cm 5 centimeters; SD 5 standard deviation.
9 9 9
Mean Median Minimum Maximum size (cm) size (cm) SD (cm) (cm) (cm) p-Value
71 5.39 107 5.07 107 4.98
6.00 6.00 6.00
3.96 3.64 3.68
0 0 0
16 16 16
0.14 0.27 0.88
R. Grazziotin Reisner et al. / Brachytherapy 14 (2015) 84e90 Table 3 Dysphagia response analysis Dysphagia score Dysphagia Dysphagia post-treatment post-treatment pretreatment Absent Liquid. NR Pasty Solid Total 1
2 0
1
2
3 NR
Absent Pasty Solid Total Solid Total Absent Liquid Pasty Solid Total Liquid Pasty Solid Total Liquid Pasty Total Liquid Total Absent Liquid NR Pasty Solid Total
1 2 10 10
2 6 6
1
3 6 2 3
6
2 6
15 16 8
12 12
6
8 8 4 4
8 9 9
4 2 1 3 13 22
1
1 2 10 13 6 6 3 6 2 15 26 6 8 12 26 9 8 17 4 4 4 1 1 3 13 23
NR 5 nonregistered.
fractions, and 38.95% in patients receiving 1800 cGy in three fractions). Sharma et al. (1) reported their experience in a large hospital in Mumbai, India, showing improved swallowing function in 43% of untreated patients and 28.5% in patients with recurrent disease, and the maintenance of pretreatment status in 41% of patients. According to the point scale created to measure the relief of dysphagia, most patients presented one-point improvement, showing a real benefit from HDRB. Our scale was similar to the scale used by Amdal et al. (34), which evaluated the benefit of brachytherapy with or without primary stent placement. Our results were quite similar to that study, with both presenting similar mean length tumor of 7 cm and most patients with one-point improvement of dysphagia. Homs et al. (35) also elaborated a dysphagia scale with different grades, varying from 0 (ability to eat a normal diet) to 4 (complete dysphagia), showing an improvement of two to three points in esophageal cancer patients treated in the Netherlands. As mentioned previously, these better results were possibly explained by a shorter mean length (6.8 cm) when compared with the mean length (7.9 cm) of this study. Although the high number of advanced lesions, complication rates observed in the present study, particularly those of bleeding and fistula (7%), were consistent with previous reports (17, 19, 27).
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It is important to notice that the most common complications (bleeding, fistula, and stricture) were not related to the location of the treatment, which could give basis to the confident use of HDRB in upper esophageal lesions. HDRB is contraindicated in cervical esophageal lesions, mainly because of the risk of fistula formation (26). In the present study, 13 patients with cervical esophageal lesions underwent HDRB with no fistula formation (Table 1). This result corroborates those obtained in a series of 91 patients, including 6 patients with cervical esophageal tumors, which showed no correlation between complication rates and tumor location; the authors concluded that fistula rates were tumor related, rather than treatment related (19). Moreover, as mentioned previously, location was not related to degree of response, giving equal chances of satisfactory response in cervical esophagus compared with other locations. It is important to notice that this study has some limitations, especially because of its retrospective nature. In addition, in some patients, it was difficult to determine if HDRB was solely the cause of stenosis, or it was also related to the tumor itself.
Conclusion In conclusion, esophageal HDRB effectively reduces dysphagia and provides rapid palliation with lower complication rates. Patients with cervical esophageal cancer can undergo palliative HDRB with no additional risk of complication.
Acknowledgments We thank Simone Reisner, Isabella Small, and Thalita da Matta de Castro for their support. References [1] Sharma V, Mahantshetty U, Dinshaw KA, et al. Palliation of advanced/recurrent esophageal carcinoma with high-dose-rate brachytherapy. [Review]. Int J Radiat Oncol Biol Phys 2002;52:310e315. [2] Yano T, Muto M, Minashi K, et al. Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: A phase II study. Int J Cancer 2012;131:1228e1234. [3] Didden P, Spaander MC, Kuipers EJ, et al. Safety of stent placement in recurrent or persistent esophageal cancer after definitive chemoradiotherapy: A case series. Gastrointest Endosc 2012;76:426e430. [4] Lindenmann J, Matzi V, Neuboeck N, et al. Individualized, multimodal palliative treatment of inoperable esophageal cancer: Clinical impact of photodynamic therapy resulting in prolonged survival. Lasers Surg Med 2012;44:189e198. [5] Aoki T, Osaka Y, Takagi Y. Comparative study of self-expandable metallic stent and bypass surgery for inoperable esophageal cancer. Dis Esophagus 2001;14:208e211. [6] Adenis A, Penel N, Horn S, et al. Palliative chemotherapy does not improve survival in metastatic esophageal cancer. Oncology 2010; 79:46e54.
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