definitive chemo-radiotherapy for esophageal cancer; failure pattern and salvage treatments ryuta...

Definitive chemo-radiotherapyfor esophageal cancer;

failure pattern and salvage treatments

Ryuta Koike, Y. Nishimura, K. Nakamatsu,

S. Kanamori, M. Okubo, K. Hiroi, T. Shibata

　　　　　 T. Nishikawa, 　 H. Shiozaki* Department of Radiation Oncology and Surgery*,

Kinki University School of Medicine

・ Failure pattern in definitive 　chemoradiotherapy (CRT) for esophageal cancer were analyzed to evaluate the appropriateness of our RT field.

Purpose

Patients Characteristics From 1999 to 2006, 136 consecutive patients with

esophageal cancer with localized esophageal cancer were treated with definitive CRT at our hospital.

Age ； 38 ~ 82 years old （ median; 64 years ）Gender; men ： females =116 ： 20PS 0/ 1/ 2 /3= 58/ 66/ 11/ 1Histology; 135 pts squamous cell carcinomas 1 pt adenocarcinomaStage; I ： II ： III: IV= 8 ： 25 ： 76: 27 (2002 UICC) T Factor T1:T2:T3 ： T4 =15:20:27 ： 74, N Factor N0 ： N1 = 27 ： 109Location of primary tumor: Ce: Ut: Mt: Lt = 19: 27: 71: 19Tumor length ： 1 ~ 19cm （ median 6.5cm ）

Initial RT Fields according to the primary site

・ Cervical esophagus (Ce)Bilateral neck and subcarinal LNs 　　　　　　　 (Short T-shaped Field)

・ Upper (Ut) and middle (Mt) esophagusBilateral neck and whole mediastinal LNs 　　　　　　　　　　　(T-shaped Field)

・ Lower esophagus (Lt)　　 Whole mediastinal LNs and perigastric LNs 　

(I-shaped Field)

Initial RT Fields

Ce Ut, Mt Lt

Radiation and Chemotherapy・ Radiation 　 therapy 60 Gy/30 fr/7 w (one-week split) for the both groups. 　 Either a 6 MV or 10 MV X-ray was used.　 Boost was given following 40 Gy.

・ Two courses of concurrent CT were combined with RT Ⅰ、 low-dose protracted pattern 　 102 pts （ 75% ）

　 CDDP 7mg/m2 　 × 　 10 days　　 5-FU 　 250-300mg/m2 　 × 　 14 days 　

Ⅱ、 high-dose pattern 　　　　　　　　　 34 pts （ 25% ） CDDP 70mg/m2 　 × 　 1 day

　　 5-FU 　　 700mg/m2 　 × 　 5 days 　

After CRT, 1-2 courses of adjuvant CT of cisplatin/5-FU were given for 75 pts (55%).

Results 　・　 A total dose of 60 Gy could be delivered for 133

pts (98%). ・　 2 courses of planned CT could be combined

concurrently with RT for 118 pts (87%). ・　 Complete response （ CR ） in the RT field

was achieved in 84 pts （ 62% ） . 　　　　　　　　 T1 　　　　　 15/15 （ 100% ）　　　　　　　　 T2 　　　　　 18/20 　（ 90% ）　　　　　　　　 T3 　　　　　 20/27 　（ 74% ）　　　　　　　　 T4 　　　　　 31/72 　（ 42% ）・ Failure Pattern of the 84 pts with CR was

evaluated.

Overall　survival 　　T1N0M0

0

.2

.4

.6

.8

1

0 10 20 30 40 50 60 70時間

n=82-year survival 　　 100 ％5-year survival 　　 80 ％

month

0

.2

.4

.6

.8

1

0 10 20 30 40 50 60 70 80 90時間

Overall　survival 　 stages　II-III　(excluding　T4)

n=392-year survival 　　59%5-year survival 　　41%

month

0

.2

.4

.6

.8

1

0 10 20 30 40 50 60 70 80 90時間

Overall　survival,　stages　III-IV 　

T4　or　M1- ｌｙｍｐｈ

n=842-year survival 　　26%5-year survival 　　19%

month

0

.2

.4

.6

.8

1

0 20 40 60 80 100

CR (n=84)

Overall　survival　rate　;　1999-2006

2-year survival 　66%5-year survival 　52%

Non-CR (n=52)

month

Failure pattern (n=84)

No rec. 　 　 39 pts (46%) 　

In-field rec.　　 12 pts (14%)

Out-field rec.33 pts (40%)

Isolated marginal rec.9 pts (11%)

Distant meta±regional LN Rec. 24 pts (29%)

Treatment results for 9 pts with isolated marginal recurrences

Lower esophageal （ out of RT Field ） rec. ２　 pts （ Origin: Ce 、 Ut ） Salvage surgery was performed for 2 pts. 　　　　　　　　　　　　　　　　　　⇒ Local control could be achieved

Lymph node rec. (out of RT Field) ７　 ptsPerigastric LN recurrence 　　　　 4 pts

　 Lymph node dissection 2 ｐｔｓ 2nd-CRT(50-60Gy) 　 2 ｐｔｓ

　 　　　　　 　　　　　　　　　⇒ Local control could be achieved

Hilar LN rec. 　 2 ptsNeck + retrocrural LNs 　 １ pt

2nd-CRT(50-60Gy) 3 ｐｔｓ 　　　　　　　　　　　　　　　 Local control could not be achieved.

In all 6 pts with lower esophageal or perigastric LNs In all 6 pts with lower esophageal or perigastric LNs recurrence,recurrence, salvage treatments were successful.salvage treatments were successful.

Local control could be achieved

Local control could be achieved

Local control could not be achieved.⇒

Late toxicities (n=84) RTOG/EORTC *: CTCAE version 3.0

• Grade G1 G2 G3 G4 =>G2 • Esophagus 3 4 5 0 9 (11%)• Heart 17 0 1 1 2 (2%)• Lung 17 3 2 0 5 (6%)• Spinal cord 1 0 0 0 0 (0%)• Pleural* 18 0 1 0 1 (1%)• Hypothyroid* 1 3 1 0 4 (5%)• Renal failure* 　 0 0 0 1 1 (1%)• Pt. Max. # 28 9 8 2 19 (23%)

ConclusionsThe 5-year overall survival rates of

definitive CRT of 60Gy for both resectable and unresectable esophageal cancer were excellent.

Although recurrences after initial CR were noted frequently, salvage treatments were successful for isolated marginal recurrences in the lower esophagus or perigastric LNs.

For Ce, Ut and Mt tumors, lower esophageal and perigastric LN region can be excluded from the initial RT field.