Brachytherapy 11 (2012) 130e136

Comparison of efficacy and safety of low-dose-rate vs. high-dose-rateintraluminal brachytherapy boost in patients with superficial

esophageal cancer

Tomoaki Tamaki1,*, Hitoshi Ishikawa1, Takeo Takahashi1, Yoshio Tamaki2,Yoshizumi Kitamoto3, Masahiko Okamoto2, Shin-ei Noda1, Hiroyuki Katoh1, Katsuyuki Shirai1,

Hideyuki Sakurai4, Takashi Nakano11Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan

2Department of Radiation Oncology, Gunma Prefectural Cancer Center, Ohta, Japan3Department of Radiation Oncology, Takasaki General Medical Center, Takasaki, Japan

4Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan

ABSTRACT PURPOSE: To compare the efficacy and the i

Received 28 Mar

accepted 23 May 201

This research was

Gunma University Gr

Maebashi, Gunma, 3

Oncology, Gunma Pre

Ohta, Gunma, 373-082

There are no actu

* Corresponding

University Graduate S

Gunma 371-8511, Jap

E-mail address: t

1538-4721/$ - see fro

doi:10.1016/j.brach

ncidence of complications of high-dose-rate (HDR)and low-dose-rate (LDR) intraluminal brachytherapy (IBT) boost after external beam radiationtherapy in patients with superficial esophageal cancer.METHODS ANDMATERIALS: Fifty-four consecutive patients with Stage I thoracic esophagealsquamous cell carcinoma who were treated with definitive radiotherapy using IBT between 1991and 2007 were studied retrospectively. LDR-IBT and HDR-IBT were performed for 19 and 35patients, respectively. After external beam radiation therapy of 56e60 Gy with a conventionalfractionation, LDR-IBT (5 Gy� 2) or HDR-IBT (3 Gy� 3) was given within 2 weeks. The medianfollow-up was 47 months (7e151 months).RESULTS: Overall, the 5-year overall survival, cause-specific survival (CSS), and locoregionalcontrol (LRC) rates were 61%, 86%, and 79%, respectively. The 5-year overall survival, CCS,and LRC rates did not differ significantly between the LDR-IBT and HDR-IBT groups (68% vs.58% ( p5 0.50), 83% vs. 85% ( p5 0.63), and 84% vs. 75% ( p5 0.42), respectively). Salvagetreatment was given in 8 locally recurrent patients, and 6 patients were rescued. The Grade $2 latemorbidities of esophagus and heart/lung were observed in 5 patients (4 in the LDR-IBT group and 1in the HDR-IBT group) and 2 patients (one from each group), respectively.CONCLUSIONS: In view of the safety profile and effectiveness, our results encourage thecontinued adoption of HDR-IBT as radiation boost in medically inoperable or elderly superficialesophageal cancer patients undergoing definitive radiotherapy. � 2012 American BrachytherapySociety. Published by Elsevier Inc. All rights reserved.

Keywords: Superficial esophageal cancer; Intraluminal brachytherapy; Dose rate

ch 2011; received in revised form 23 May 2011;

1.

conducted in the Department of Radiation Oncology,

aduate School of Medicine (3-39-22, Showa-machi,

71-8511, Japan) and the Department of Radiation

fectural Cancer Center (617-1 Takahayashinishi-cho,

8, Japan).

al or potential conflicts of interest.

author. Department of Radiation Oncology, Gunma

chool of Medicine, 3-39-22 Showa-machi, Maebashi,

an. Tel.:þ81-27-220-8383; fax: þ81-27-220-9397.

amakit@med.gunma-u.ac.jp (T. Tamaki).

nt matter � 2012 American Brachytherapy Society. Publis

y.2011.05.008

Introduction

With the advancement of endoscopic techniques, such asapplication of iodine dye, magnifying endoscopy, andnarrow-band imaging, increasing number of esophagealcancer patients are detected at an early stage in recent yearsin Japan (1), where up to 30% of all esophageal cancers aresuperficial cancers (2, 3). Although the standard treatmentfor both early-stage esophageal cancer and advanceddisease is a definitive esophagectomy with lymph nodedissection (4e7), a significant portion of the patients arenot able to receive surgery because of other confoundingfactors, such as the advanced age and coexisting medical

hed by Elsevier Inc. All rights reserved.

Table 1

Characteristics of patients

Patient

characteristics Total

Number of patients

in IBT groups, n (%)

p-ValueLDR IBT HDR IBT

Gender

Male 44 14 (74) 30 (86) 0.47

Female 10 5 (26) 5 (14)

Age

!70 23 7 (37) 16 (46) 0.53

$70 31 12 (63) 19 (54)

Performance status

0 22 7 (37) 15 (43) 0.67

1e2 32 12 (63) 20 (57)

Location

Upper thoracic 11 3 (16) 8 (23) 0.54

Middle thoracic 33 11 (58) 22 (63)

Lower thoracic 10 5 (26) 5 (14)

Tumor length (cm)

#5 39 14 (74) 25 (71) 0.86

O5 15 5 (26) 10 (29)

T classification

T1a 8 2 (11) 6 (17) 0.80

T1b 46 17 (89) 29 (83)

Total dose (Gy) 67.8� 2.1 67.6� 3.7 67.9� 1.8 0.77

Reason for RT

Medically inoperable 42 12 (63) 30 (86) 0.12

Refusal of surgery 12 7 (36) 5 (14)

IBT5 intraluminal brachytherapy; LDR5 low-dose-rate; HDR5 high-

dose-rate; RT5 radiotherapy.

131T. Tamaki et al. / Brachytherapy 11 (2012) 130e136

issues. For medically inoperable superficial esophagealcancer (SEC) patients, external beam radiation therapy(EBRT) with or without concurrent chemotherapy isanother treatment option. We have previously reported theefficacy of intraluminal brachytherapy (IBT) for SECpatients and have shown that EBRT combined with IBTyields an excellent local control and survival, even formedically inoperable patients (8e10).

Although low-dose-rate (LDR) brachytherapy is consid-ered to produce less adverse effects on normal tissue whiledelivering adequate dose to the target, high-dose-rate(HDR) brachytherapy has many advantages. These includethe ability to create a favorable dose distribution usingwell-optimized treatment planning, shorter treatment timeper session, and avoidance of radiation exposure to medicalpersonnel. For the treatment of cervical cancer, an intenseeffort has been made to compare the results of the LDRand HDR intracavitary brachytherapy, and most reportshave concluded that the intracavitary brachytherapy usingtwo different dose rates can yield almost equal clinicalresults with similar incidence of complications (11). Onthe other hand, few reports have focused on the differencein dose rate in the brachytherapy of esophageal cancer,although IBT has been used as a boost therapy for SECpatients (8e10, 12e21). A previous report has comparedthe effectiveness of LDR-IBT and HDR-IBT for theimprovement of dysphagia in patients with advancedesophageal cancer and has concluded that these twomethods are equally effective (22). However, the compar-ison of efficacy and incidence of late complications in thecurative treatment using uniform protocols has beenlacking.

In our previous report that showed the usefulness of IBTcombined with EBRT for SEC, the effect of dose rate wasnot studied in patients treated with brachytherapy (10).Hence, in this report, the clinical efficacy and the incidenceof complications after definitive radiotherapy (RT) usingIBT for SEC patients were analyzed with special regardto the dose rate of brachytherapy.

Methods and materials

Patients

The characteristics of patients in this study are summ-arized in Table 1. This study retrospectively evaluated 54consecutive patients with thoracic esophageal cancer classi-fied as Stage I (T1N0M0) according to 2002 Union forInternational Cancer Control criteria (23) who were treatedwith combination therapy of EBRT and IBT between 1991and 2007 at either Gunma University Hospital or GunmaPrefectural Cancer Center. The median age of the patientswas 70 years (range, 49e86 years). Nineteen patients weretreated with LDR-IBT using cesium-137 source, and 35patients were treated with HDR-IBT using iridium-192source. The tumorswere located at the upper thoracic,middle

thoracic, and lower thoracic esophagus in 11, 33, and 10patients, respectively. Pathology examination of biopsysamples obtained with endoscopy proved that all patientshad primary squamous cell carcinoma of the esophagus.These patients received curative RT because either they wereevaluated to be medically inoperable for reasons such asadvanced age or existing complications (n5 42) or refusedsurgical treatment (n5 12). Thus, more than 75% of patientsin this study were unsuitable for curative surgery. Patientswho received HDR-IBT were more likely to be medicallyinoperable compared with LDR-IBT (Table 1). Stagingevaluation was performed by using chest X-ray, ultrasound,esophagography, endoscopic ultrasound, and CT.

External beam radiation therapy

The RT treatment policy for the present study was previ-ously described in detail (8, 9). In brief, two to four surgicalclips were placed at the tumor edges while the patientunderwent endoscopy before the initial treatment planningto identify the tumor location on treatment planning. A totaldose of 40e46 Gy by using a 10-MV photon beam withanteroposterior-opposed fields was delivered, and thenadditional irradiation was delivered using either bilateraloblique portals or more than three beam ports withshrinking fields to avoid irradiating to the spinal cord.

132 T. Tamaki et al. / Brachytherapy 11 (2012) 130e136

The median width of the initial field was 7 cm (range,6e8 cm), with a 3- to 4-cm margin from both the cranialand the caudal edges of the tumor. The radiation field forthe boost therapy was set with a 2-cm margin relative tothe location of these clips in the initial field.

In general, the total dose of EBRT prescribed was 56 Gyfor T1a patients (range, 56e60 Gy) and 60 Gy for T1bpatients (range, 54e64 Gy). The EBRT was delivered witha conventional daily dose of 2 Gy over 6 weeks and wasfollowed by LDR-IBT or HDR-IBT.

Intraluminal brachytherapy

The technique of IBT was also described previously(8e10). LDR-IBT had been administered to 19 patientsbetween 1991 and 1996. Subsequent to this, HDR-IBTwas initiated because of the renovation of brachytherapyfacilities in the two institutions and has been used routinelysince 1997 (n5 35). A rubber gastric tube with 10 mm indiameter was used for LDR-IBT, and a 15- or 20-mm outerdiameter commercial double-lumen-balloon applicator wasused for HDR-IBT. The reference point for dose calcula-tion was a point at a distance of 5 mm from the applicatorsurface. LDR-IBT was delivered with a fractional dose of5 Gy, given once per week at a total dose of 10 Gy,whereas HDR-IBT was given with a fractional dose of3 Gy, twice per week at a total dose of 9 Gy. However,two initial cases receiving HDR-IBT were treated withthe same treatment protocol as that used for LDR-IBT (2fractions of 5 Gy).

Table 2

Comparison of outcomes according to treatment methods

Outcomes

Total

(n5 54),

n (%)

Number of patients

in each group, n (%)

p-

Value

LDR IBT

(n5 19)

HDR IBT

(n5 35)

All recurrences

Yes 11 (20) 3 (16) 8 (23) 0.79

No 43 (80) 16 (84) 27 (77)

Locoregional

recurrences

Yes 10 (19) 3 (16) 7 (20) 0.98

No 44 (81) 16 (84) 28 (80)

Distant metastasis

Yes 1 (2) 0 (0) 1 (3) 0.75

No 53 (98) 19 (100) 34 (97)

Treatment-related death

Yes 2 (4) 1 (5) 1 (3) 0.76

No 52 (96) 18 (95) 34 (97)

Survival

Alive 29 (54) 7 (37) 22 (63) 0.12

Dead 25 (46) 12 (63) 13 (37)

Disease specifica 6 (11) 3 (16) 3 (9) 0.72

From other diseases 19 (35) 9 (47) 10 (29)

LDRIBT5 low-dose-rate intraluminal brachytherapy;HDRIBT5 high-

dose-rate intraluminal brachytherapy.a Treatment-related death is included.

Followup examination

The median follow-up period was 47 months (range,7e151months). The follow-up examination included a phys-ical examination and the measurement of a serum tumormarker of squamous cell carcinoma antigen; measurementswere taken at 1-month interval during the first year after RTand then at 1- to 3-month intervals thereafter. Esophagogra-phy and endoscopy were performed for assessment of thetumor response at 1 month after completion of RT. Theseexaminations were repeated every 3 months during the firstyear and every 6 months thereafter. When a local recur-rence was suspected, endoscopic biopsy was performedfor pathologic confirmation. CT scans were performedroutinely in all patients for evaluation of tumor recurrencein the lymph nodes (LNs) and distant organs at 6-month inter-vals during the first 3 years after RT. Locoregional recurrencewas documented for either tumor recurrence in the esophagusor regional LNs.

Complication of RT was assessed according to theNational Cancer Institute’s Common Terminology Criteriaof Adverse Effect, version 3, and the Radiation TherapyOncology Group/European Organization for Research andTreatment of Cancer late morbidity scoring schema (24).

Statistics

Comparison of data was analyzed by Fisher’s exact t testor Yates’ continuity-corrected chi-squared test. The overallsurvival (OS), cause-specific survival (CSS), and locore-gional control (LRC) rates were calculated from the dateof the start of RT to the patient’s death or to the last followupaccording to the Kaplan-Meier method (25). The survivalcurves were compared by the log-rank test as a univariateanalysis.

Results

Outcomes

Table 2 summarizes clinical outcomes according to thetreatment method. Tumor recurrences were observed in 11patients (20%) in total. Among them, 10 patients hadlocoregional recurrences (3 [16%] in the LDR-IBT groupand 7 [20%] in HDR-IBT group), and only 1 patient inHDR-IBT group had recurrence at a distant site (lung). Therewere total of 25 deaths; 6 from esophageal cancer including 2treatment-related deaths and 19 from other diseases withoutany recurrences. Eleven (58%) of the 19 patients died of othercancers; the types of the cancers were lung cancer (n5 3),gastric cancer (n5 3), hypopharyngeal cancer (n5 2),bladder cancer (n5 1), cancer of the floor of mouse(n5 1), and prostate cancer (n5 1). These cancers wereevaluated to be second cancers and not recurrences of esoph-ageal cancer because of pathological diagnoses and clinical

Table 3

Comparison of 5-year LRC, CSS, OS rates (average� SD, %)

Outcomes LDR IBT HDR IBT p-Value

All cases (n5 54) n5 19 n5 35

5-y LRC 83.5� 17.1 75.0� 18.5 0.42

5-y CSS 83.0� 17.6 84.9� 18.8 0.63

5-y OS 68.4� 20.9 58.0� 20.1 0.50

T1b cases (n5 46) n5 17 n5 29

5-y LRC 81.5� 19.1 72.9� 21.3 0.51

5-y CSS 80.8� 19.6 81.5� 9.2 0.72

5-y OS 64.7� 22.7 53.6� 20.1 0.50

133T. Tamaki et al. / Brachytherapy 11 (2012) 130e136

courses of the diseases. The OS, CSS, and LRC of the totalpatients are shown in Fig. 1. The 5-year OS, CSS, and LRCrates were 61% (95% confidence interval [CI]: 47e75%),85% (95% CI: 76e93%), and 79% (95% CI: 67e92%),respectively.

The 5-year LRC, CSS, and OS for LDR-IBT group andHDR-IBT are compared in Table 3. In the analysis of bothtotal cases (T1a and T1b combined, n5 54) and T1b casesonly (n5 46), the 5-year LRC, CSS, and OS did not differsignificantly between LDR-IBT group and HDR-IBTgroup.

LRC5 locoregional control; CSS5 cause-specific survival; OS5 over-

all survival; SD5 standard deviation; LDR IBT5 low-dose-rate intralumi-

nal brachytherapy; HDR IBT5 high-dose-rate intraluminal brachytherapy.

Salvage therapy for recurrence

The details of the recurrent patients are shown in Table 4.Of the 11 recurrent patients, 10 were local recurrences;4 tumors were superficial tumors and 6 were advancedtumors. Salvage treatment was able to be given in 8 patients:3 with surgery, 2 with endoscopic mucosal resection, 2 withargon plasma-laser coagulation, and 1 with photodynamictherapy. Among the 3 patients who underwent salvageoperation for local tumor recurrence, 2 patients initiallyrefused surgery and received RT as the primary treatment.The other one patient was regarded as medically inoperablepatient for curative surgery as the primary treatment becauseof renal failure by uncontrolled diabetes mellitus. Becausethe local recurrent tumor invaded into the muscular layerof esophageal wall but no apparent lymph node metastasiswas detected, the patient received transhiatal esophagectomywithout lymph node dissection as the salvage operation. Sixpatients were rescued by the salvage treatment; all 4 patientswith superficial local recurrent tumors were treated withendoscopic mucosal resection or argon plasma-laser coagu-lation and rescued, whereas 2 of 4 (50%) patients treatedwith surgery or photodynamic therapy for locally advancedrecurrences were rescued.

Figure 1. Curves for overall survival, cause-specific survival, and locore-

gional control of Stage I thoracic esophageal cancer patients undergoing

curative treatment with external beam radiotherapy and intraluminal

brachytherapy.

Late morbidity

Late complications according to the treatment group areshown in Table 5. The Grade 2 or higher complications ofesophagus were observed in the total of 5 patients, 4 inLDR-IBT group, and 1 in HDR-IBT group ( p5 0.03).All 5 patients developed esophageal ulcer, and 2 of themprogressed to esophageal fistula (one from each group)and died of pneumonia. The patient who developed esoph-ageal fistula after LDR-IBT had a 12-cm primary lesion inthe middle lower thoracic region and had been on hemodi-alysis for chronic renal failure. The patient who developedesophageal fistula after HDR-IBTwas treated with a higherfraction dose of 5 Gy (8), and no esophageal ulcers wereobserved after the current fractionation (3 Gy� 3) wasadopted for HDR-IBT treatment. Grade 2 or higher cardio-respiratory complications were observed in 2 patients, onefrom each group.

Discussion

In this study, the 5-year OS, CSS, and LRC rates of all ofthe patients were 61%, 85%, and 79%, respectively. Therewere no statistical differences in 5-year LRC, CSS, and OSbetween the LDR-IBT and the HDR-IBT groups (Table 3).In addition, EBRT combined with either LDR-IBT orHDR-IBT for SEC patients were equally effective in thetumor control and the survival irrespective of tumor stage.Previously, the comparison of clinical results betweenLDR and HDR brachytherapy has been investigated inpatients with the uterine cervical cancer, head and neckcancers, and soft-tissue sarcomas (11, 26e29), and thesereports have shown that no obvious difference in safetyand tumor control according to the dose rates inbrachytherapy.

In esophageal cancer, the clinical results between LDRand HDR brachytherapy were previously compared in thepalliation of dysphagia for advanced tumors, and there wasno difference between treatments with HDR or LDR (22).On the other hand, some studies have used IBT as a boosttherapy with definitive RT (8e10, 12e21) but did not

Table 4

Characteristics of recurrent cases

Case

Recurrence

pattern

Time after

RT (mo) Age T factor

Tumor

length (cm) PS

Total dose

(Gy) Salvage treatment/result

LDR IBT

1 Local/insidea 13 76 T1b 15 1 68 Inoperable

2 Local/inside 25 68 T1b 4 1 70 Inoperable

3 Local/inside 62 62 T1b 6 0 70 Surgery/rescued

HDR IBT

1 Local/inside 10 72 T1b 4 1 69 APC/rescued

2 Local/inside 18 77 T1b 5.5 1 69 EMR/rescued

3 Local/inside 39 65 T1b 4 2 63 Surgery/rescued

4 Local/inside 14 58 T1b 7 0 69 Surgery/recurred

5 Local/inside 46 81 T1b 4 1 69 PDT/recurred

6 Local/outsideb 6 79 T1a 4.5 1 65 EMR/rescued

7 Local/outside 70 67 T1b 3 1 73 APC/rescued

8 Distant (lung) 4 68 T1b 8 1 69 d

RT5 radiotherapy; PS5 performance status; LDR IBT5 low-dose-rate intraluminal brachytherapy; HDR IBT5 high-dose-rate intraluminal

brachytherapy; PDT5photodynamic therapy; EMR5endoscopic mucosal resection; APC5argon plasma-laser coagulation.a Local recurrence inside the irradiated field.b Local recurrence outside the irradiated field.

134 T. Tamaki et al. / Brachytherapy 11 (2012) 130e136

compare between LDR-IBT and HDR-IBT in detail. Thepresent study used similar standard treatment protocols thatroutinely combined IBT and EBRT. Because of this consis-tency in other treatment parameters between patients, thisis a unique opportunity to analyze the effect of dose rateon the feasibility and effectiveness of IBT on SEC patients.To our knowledge, this is the first report comparing theeffects of HDR-IBT with LDR-IBT in RT for SEC patients.

With regard to late morbidity, LDR-IBT and HDR-IBTboth resulted in the comparable or lower incidence of latecomplications in heart/lung when compared with previousreports of EBRT alone (8, 19) or EBRT combined withchemotherapy (30e32) in definitive RT for esophagealcancer. However, radiation-induced esophageal ulcer wasobserved in 4 (21%) of 19 cases of the LDR-IBT group butin 1 (3%) of 35 cases of the HDR-IBT group. Of note is thata previous review comparing studies using LDR-IBT andHDR-IBT found that LDR-IBT was less likely to causesevere complications in the treatment of esophageal cancer(33); however, in this present study, HDR-IBT caused lessesophageal ulcers compared with LDR-IBT ( p5 0.03).Because the HDR-IBT group in this study included moremedically inoperable patients who had rather unfavorablemedical conditions compared with the LDR-IBT group(Table 1), this result requires further discussion. Thedifferent study conclusions observed may be because of

Table 5

Comparison of late complications (Grade $2)

Category

LDR IBT

(n5 19), n (%)

HDR IBT

(n5 35), n (%) p-Value

Esophagus 4 (21) 1 (3) 0.03

Heart/lung 1 (5) 2 (6) 0.95

LDRIBT5 low-dose-rate intraluminal brachytherapy;HDRIBT5 high-

dose-rate intraluminal brachytherapy.

several factors. First, the dose per fraction of IBT may affectthe occurrence of the esophageal ulcer. The dose per fractionof LDR-IBTwas 5 Gy, whereas that of HDR-IBTwas 3 Gy,with the exception of the first 2 patients in our study.Although one of the first 2 patients who received HDR-IBTwith a dose per fraction of 5 Gy had a radiation-inducedesophageal fistula with no evidence of tumor recurrence,there were no significant esophageal complications whenpatients who received HDR-IBT with a dose per fraction of3 Gy. Today, the guideline by the Japanese Society forTherapeutic Radiology and Oncology recommends 4 Gy orlower per fraction when using IBT for treatment of esop-hageal cancer (19). Yorozu et al. (14) also reported that theHDR-IBT results in a lower incidence of esophageal compli-cations when the higher dose per fraction is avoided. Second,the use of balloon-type applicators with larger diametersmay also prevent the excessive dose to the mucosal surfaceand reduce the incidence of esophageal ulcers (14, 15).In our institutions, a rubber gastric tube with 10 mm indiameter was used for LDR-IBT, but a double-lumen appli-cator in 15- or 20-mm diameter was used for HDR-IBT.Therefore, both of smaller dose per fraction and superiordose distribution because of the use of balloon-type appli-cator may have resulted in the lower incidence of esophagealcomplications in HDR-IBT compared with LDR-IBT in thisstudy.

A clear advantage of using HDR-IBT technique is theavoidance of radiation exposure to the medical personnel.Another advantage is the shorter treatment time for each bra-chytherapy session. Although the average treatment sessionof LDR-IBT for esophageal cancers takes approximately 3hours, that for HDR-IBT is only approximately 30 minutesincluding the time for treatment planning. The differencemay result in better compliance and safety especially forelderly patients or inoperable patients. Furthermore, the

135T. Tamaki et al. / Brachytherapy 11 (2012) 130e136

shorter treatment time using HDR-IBT may prevent theapplicator from deviating from its preplan position andenable more accurate irradiation of the tumor and betterlocal control.

From our previous analysis of the clinical results of SECpatients receiving RT, the application of boost therapy usingIBT improved the local control and survival (10). It has beenknown that concurrent chemoradiotherapy improves the clin-ical outcome of advanced esophageal cancer, but it alsoresults in higher incidence of cardiac and pulmonary compli-cations (30e32). Furthermore because there are significantnumbers of patients who are contraindicated for CRT becauseof other confounding factors, such as advanced age and coex-isting medical issues, EBRT combined with IBT may be aneffective treatment options for patients with SEC.

Our study has several shortcomingsmainly related the useof retrospective data for comparison including the followingfactors. First, any retrospective analysis is prone to bias thatmay be unnoticed or unintended. Second, the change of bra-chytherapy practice from LDR-IBT to HDR-IBT because ofthe renovation of facilities limited us to use the data of theLDR-IBT group with a relatively smaller sample size(n5 19) compared with the HDR-IBT group (n5 35),which may have lessened the statistical power of this study.Last, because the LDR-IBT group preceded the HDR-IBTgroup chronologically, technical advances over time mayhave favored the HDR-IBT group. In light of these shortcom-ings, however, it should be noted that the incidence of eso-phageal adverse effects was significantly lower for theHDR-IBT group despite the sample sizes and that factorssuch as the use of balloon-type applicators and the capacityto use optimized treatment planning are inherent advantagesof HDR brachytherapy practice as well as technical advancesover time.

Conclusions

HDR-IBT offers advantages over LDR-IBT such asshorter treatment time per session and avoidance of radia-tion exposure to medical personnel. Especially in view ofthe reported safety profile and effectiveness, our resultsencourage the continued adoption of HDR-IBT as radiationboost in medically inoperable or elderly SEC patientsundergoing definitive RT.

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