ORIGINAL ARTICLE

Esophagus (2005) 2:21–23 © Japan Esophageal Society and Springer-Verlag 2005DOI 10.1007/s10388-004-0031-3

Atsunori Yorozu

Radiotherapy for nodal recurrence after chemoradiotherapy foresophageal carcinoma

Received: July 26, 2004 / Accepted: October 23, 2004

AbstractBackground. To evaluate the treatment outcome of radio-therapy for nodal recurrence after definitive chemoradio-therapy for esophageal carcinoma.Methods. Between 1996 and 2001, ten patients with isolatednodal recurrence after definitive chemoradiotherapy re-ceived radiotherapy with or without chemotherapy. Thesite of recurrence was the mediastinum in five patients, theceliac node in four patients, and the supraclavicular fossa inone patient. All sites of nodal recurrence were outside theprevious irradiated area and without local recurrence ordistant metastases. Radiotherapy was given with three-dimensional conformal technique, and an average totaldose was 60Gy. Eight patients received chemotherapy con-currently with radiotherapy. Chemotherapy consisted oftwo cycles of cisplatin and 5-FU.Results. The control rate of the irradiated region was eightof ten patients. The size of all controlled lesions was 3cm orless in diameter. In five patients, distant metastases devel-oped to other organs and caused death. Two patients sur-vived without disease for 5 years and three patients survived2 years or more. In four patients with an interval of 2 yearsor longer between the previous treatment and nodal recur-rence, three patients survived without disease. Improve-ment of clinical symptoms such as dysphagia or hoarsenesswas obtained in five of six patients.Conclusions. Radiotherapy for isolated nodal recurrence ofesophageal carcinoma after definitive chemoradiotherapy issuggested to be safe and effective. This treatment is pro-mising as well as palliative.

Key words Esophageal cancer · Radiotherapy · Recurrence· Chemoradiotherapy

A. Yorozu (*)Department of Radiology, Tokyo Medical Center, National HospitalOrganization, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902,JapanTel. �81-3-3411-0111; Fax �81-3-3412-9811e-mail: ayorozu@aol.com

Introduction

After chemoradiotherapy for esophageal carcinoma, nodalrecurrence without local failure or distant metastases occursin about 9% of total treatment failure [1]. When nodalrecurrence occurs outside the previous irradiated area,radiotherapy with or without chemotherapy might curethose isolated nodal recurrences. The outcome of treatmentfor isolated nodal recurrence has not been reported yet. Weretrospectively analyzed if radiotherapy was effective forthis type of recurrence.

Methods

Between 1993 and 2001, 112 patients with esophagealcarcinoma received radiotherapy, with or without chemo-therapy, with curative intent at Tokyo Medical Center,National Hospital Organization. All patients had squamouscell carcinoma. Ninety patients received chemoradio-therapy. The details of treatment have been reported pre-viously [2,3]. The site of first recurrence was the nodalregion in 10 patients, the esophagus in 28 patients, the dis-tant metastases in 11 patients, and combination of these in16 patients. We evaluated the 10 patients with regionalnodal recurrence alone; 5 patients had recurrence in themediastinum, 4 patients in the celiac node, and 1 patient inthe supraclavicular fossa. All sites of nodal recurrence weresolitary and outside the previous irradiated area.

Diagnosis of recurrence was based on regular checkupor follow-up computed tomography (CT) findings. Theinterval between follow-up CT was 6 months in the first2 years and 12 months after 2 years. The diagnosis ofmediastinal or abdominal recurrence was based on thenode growing larger than 2cm viewed via CT. Histopatho-logical examination was not done. In six patients, changes insymptoms were evaluated; hoarseness in three patients,dysphagia in two patients, and abdominal pain in onepatient.

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All ten patients with isolated regional recurrence re-ceived radiotherapy. A linear accelerator (10, 6, or 4MV)was used as the X-ray source. The radiation field was a localfield with a margin of 1–2cm from the tumor. In all patientswith mediastinal or celiac nodes, three-dimensional confor-mal radiotherapy was used to avoid overlapping with theprevious radiation field (Fig. 1). Conventional fractionation(2Gy/fraction, 1 fraction/day, five times per week) wasused. The median radiation total dose was 60Gy (range, 50–72Gy). Eight patients received chemotherapy concurrentlywith radiotherapy. Chemotherapy consisted of two cycles ofcisplatin (60mg/m2) and 5-fluorouracil (5-FU) (600mg/m2

per 24h, continuous infusion for 5 days). Response wasevaluated by CT scan or palpation. Complete response wascomplete resolution of all clinically detectable disease for aperiod of at least 1 month by definition. Partial responsewas a reduction in tumor dimensions of at least 50% main-tained for at least 1 month. No change was a response thatis less than a partial response or progression less than a 25%increase during the period of observation.

The last follow-up was performed in July 2004. Survivalperiods were calculated from the start of irradiation tonodal recurrence.

Results

Patient and treatment characteristics are shown in Table 1.The median survival period was 2 years. Five patients sur-vived more than 2 years, and two patients were alive with-out disease after 5 years. The disease-free survival periodwas 11 months.

Complete response and partial response were observedin seven and two of the patients, respectively. Regionalcontrol in the treated area was obtained finally in eightpatients of ten. All the controlled lesions were 3cm or lessin diameter. Regrowth of the tumor in the treated areaoccurred in the two other patients and finally caused death.Distant metastases to other organs developed in five pa-tients and caused death. Three patients were free from dis-ease at the last follow-up.

In five patients with 2 years or longer between previoustreatment and nodal recurrence, four patients survivedmore than 2 years after recurrence. In the other five pa-tients, only one patient survived 2 years.

Improvement in symptoms was observed in five of the sixpatients. No late complications were observed.

Fig. 1. Case example of isodose distributions. Three-dimensional conformal radiotherapy for metastatic celiac lymph node is presented. The 95%of 60-Gy isodose line includes a 3-mm margin around the tumor

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Discussion

In the treatment of esophageal cancer with chemoradio-therapy, there is no consensus as to prophylactic irradiationto three fields: the neck, the mediastinum, and the abdomi-nal nodal region. Actually, the incidence of local failureafter chemoradiotherapy is still high [1,2] . Long-term se-vere complications of pulmonary or cardiac function havebeen reported [4]. In practice, the superior and inferiorborders of the radiation field are often 3cm or 5cm beyondthe primary tumor, or sometimes include regional nodes[1–3]. The number of patients with nodal recurrence with-out local disease or distant metasetases will increase in thenear future. Radiotherapy or surgery is anticipated to sal-vage the isolated nodal recurrence. We reported curabilitywith radical radiotherapy for this type of recurrence.

We treated metastatic lymph nodes sized between 2 and4cm. The size of tumor is important for radiotherapy, andlong-term follow-up must be important for those patients.The size of all controlled lesion was 3cm or less in diameter.We were unable to evaluate whether chemotherapy waseffective because of the small number of patients. Fivepatients developed distant metastases to other organs.Chemotherapy will be reexamined in the future. The timeinterval between surgery and the onset of recurrence wasreported to be the prognostic factor [5]. The time intervalbetween the initial treatment and onset of recurrence seemsthe prognostic factor for chemoradiotherapy as well. Wefound no complications of treatment.

In conclusion, radiotherapy with or without chemo-therapy for isolated nodal recurrence after definitive radio-therapy is effective. The prognosis of the patients who hadrecurrence after 2 years was good. Further investigation isrequired to confirm this result.

References

1. Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TH, Martenson J,Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group94-05) Phase III trial of combined-modality therapy for esophagealcancer: high-dose versus standard-dose radiation therapy. J ClinOncol 2002;20:1167–74.

2. Yorozu A, Dokiya T, Oki Y, Suzuki T. Curative radiotherapy withhigh-dose-rate brachytherapy boost for localized esophageal carci-noma: dose-effect relationship of brachytherapy with the balloontype applicator system. Radiother Oncol 1999;51:123–9.

3. Yorozu A, Dokiya T, Oki Y. High-dose-rate brachytherapy boostfollowing concurrent chemoradiotherapy for esophageal carcinoma.Int Radiat Oncol Biol Phys 1999;45:271–5.

4. Nemoto K, Ariga H, Kakuto Y, Matsushita K, Takeda C, TakahashiY, et al. Radiation therapy for loco-regionally recurrent esophagealcancer after surgery. Radiother Oncol 2001;61:165–8.

5. Ishikura S, Nihei K, Ohtsu A, Boku H, Hironaka S, Mera K, et al.Long-term toxicity after definitive chemoradiotherapy for squa-mous cell carcinoma of the thoracic esophagus. J Clin Oncol 2003;15:2697–702.

Tab

le 1

.C

hara

cter

isti

cs o

f pa

tien

ts a

nd t

umor

s

Pat

ient

Age

Sex

cTN

MT

umor

Site

of

noda

lT

ime

toSy

mpt

omSi

ze o

fR

adia

tion

Che

mot

hera

pyE

ffec

tR

elap

seP

rogn

osis

num

ber

loca

tion

recu

rren

cere

curr

ence

lesi

on (

cm)

dose

(G

y)

168

MT

3N1

Ut

Cer

vica

l4

year

sD

ysph

agia

3.5

60Y

esP

RR

egro

wth

Dea

d of

dis

ease

aft

erpa

raes

opha

geal

1 ye

ar2

70F

T1N

0M

tP

retr

ache

al3

year

sH

oars

enes

s2

72N

oC

RN

o re

curr

ence

Aliv

e w

itho

ut d

isea

seaf

ter

7 ye

ars

366

MT

2N0

Mt

Supr

acla

vicu

lar

1 ye

arN

one

250

Yes

CR

No

recu

rren

ceA

live

wit

hout

dis

ease

afte

r 5

year

s4

61F

T3N

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tU

pper

tho

raci

c3

year

sD

ysph

agia

366

Yes

CR

Met

asta

ses

to p

leur

a,D

ead

of d

isea

se a

fter

para

esop

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albo

ne, l

iver

aft

er 2

yea

rs3

year

s an

d 10

mon

ths

545

MT

1N0

Mt

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iac

5 ye

ars

Non

e3

60N

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live

r,D

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se a

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aort

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aft

er1

year

and

6 m

onth

s1

year

656

MT

3N1

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iac

11 m

onth

sN

one

250

Yes

CR

Met

asta

ses

to li

ver

Dea

d of

dis

ease

aft

eraf

ter

5 m

onth

s1

year

770

FT

3N1

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Cel

iac

11 m

onth

sA

bdom

inal

pai

n3.

560

Yes

NC

Reg

row

thD

ead

of d

isea

se a

fter

1 ye

ar8

45F

T3N

1M

tC

elia

c2

year

sN

one

360

Yes

CR

No

recu

rren

ceA

live

wit

hout

dis

ease

afte

r 2

year

s9

70M

T3N

1M

tU

pper

10 m

onth

sH

oars

enes

s2.

560

Yes

PR

Met

asta

ses

to li

ver,

lung

Dea

d of

dis

ease

aft

erm

edia

stin

alaf

ter

4 m

onth

s8

mon

ths

1071

MT

3N1

Mt

Upp

er11

mon

ths

Hoa

rsen

ess

266

Yes

CR

Met

asta

ses

to lu

ng a

fter

Aliv

e w

ith

dise

ase

afte

rm

edia

stin

al6

mon

ths

2 ye

ars

Ut,

uppe

r th

orac

ic p

orti

on o

f in

trat

hora

cic

esop

hagu

s; M

t, m

iddl

e th

orac

ic p

orti

on; L

t, lo

wer

tho

raci

c po

rtio

n; P

R, p

arti

al r

espo

nse;

CR

, com

plet

e re

spon

se; N

C, n

o ch

ange