Initial Experience of Bladder Preservation Therapy Using ...

4 downloads 102 Views 2MB Size Report
of Bladder Preservation. Therapy. Using Chemoradiotherapy with Regional. Hyperthermia for Muscle-invasive. Bladder Cancer. TAKAYUKI. OHGURI*,. HAJIME.
Regional

Original

Hyperthermia

for

Bladder

Cancer •E

T.

Ohguri

et

al.

Contribution

Initial Experience of Bladder Therapy Using Chemoradiotherapy Hyperthermia for Muscle-invasive TAKAYUKI FUMIO

OHGURI*,

KATO,

KATSUYA

KEITA Department

HAJIME

YAHARA,

NAKANO,

of Radiology,

IMADA,

organ-preserving

SATOSHI

TOMOAKI

YUKUNORI

University

regimens

using

NOMOTO, MORIOKA,

KOROGI

of Occupational

Health. Kitakyushu-shi,

Abstract : Recently,

Preservation with Regional Bladder Cancer

and Environmental

Japan

predominantly

multiple-modality

therapy , consisting of endoscopic transurethral resection followed by irradiation with concurrent chemotherapy, are emerging as viable alternatives for muscle-invasive bladder cancer, although radical cystectomy has been the standard treatment. Three cases with muscle-invasive bladder cancer (5-7 cm in size) , two of T2N1M0 and one of T2NOMO, underwent bladder preservation therapy with regional hyperthermia for improvement of the local effect. A total dose of 66-7OGy in the conventional methods , chemotherapy composed

of methotrexate,

doxorubicin,

cisplatin

and/or

vinblastine,

and 3 to

12 sessions of

hyperthermia during radiotherapy were delivered. All three cases showed complete response without any local recurrence or distant metastasis in follow-ups. Toxicity during the treatment was acceptable, and late toxicity was not recognized.

Bladder preservation therapy adding regional hyperthermia is

potentially useful for improving the treatment results for muscle-invasive bladder cancer of large tumor size. Key word : bladder cancer, chemotherapy, hyperthermia, radiotherapy Introduction Muscle-invasive tumors comprise 20 % to 25 % of all newly diagnosed bladder cancerso.

The most

appropriate treatment algorithm for muscle-invasive bladder cancer remains controversial. Although radical cystectomy has been the standard treatment for two decades, organ-preserving regimens using predominantly multiple-modality therapy, consisting of endoscopic transurethral resection (TUR) followed by irradiation with concurrent chemotherapy, are emerging as viable alternatives in a subset of patients. A major limitation of pelvic external beam radiation therapy is that the dose required to achieve an adequate level of local control in such tumors exceeds the tolerance of the surrounding normal tissues . Received 9 Febrary 2005, Accepted 8 March 2005. *Corresponding E-mail : [email protected]

author, Tel : +81-93-691-7264 ; Fax : 4-81-93-692-0249 ;

151

( 23 )

Jpn. J. Hyperthermic Oncol. 21 (3) : 2005

日本 ハ イ パ ー サ ー ミ ア 誌21〔3〕:(平

成17年)

Hyperthermia has been used in combination with radiation therapy and/or chemotherapy, and considered to be effective for certain type of tumors2-6). Treatment results of radiotherapy and/or chemotherapy plus hyperthermia for bladder cancer were also reported7-12). Improvement of the local effect by hyperthermia is especially expected in large tumors.

In the present three cases, bladder

preservation therapy, consisting of TUR followed by irradiation with concurrent chemotherapy and regional hyperthermia, was used to treat with muscle-invasive bladder cancer of large tumor size. Materials and methods Patients Between January 2000 and December 2002, three patients with invasive bladder cancer were treated with chemoradiotherapy

plus regional hyperthermia at our hospital.

Characteristics and treatments of

patients are given in Table I. TUR was used for both diagnosis and treatment as reducing the tumor volume in all the three patients. Acute toxicity was scored according to criteria of radiation therapy oncology group13). Late toxicity was mainly investigated by a telephone to the patients or their family. Table

I

Characteristis

SCC : squamous (doxorubicin),

of patients

cell carcinoma, CDDP

and treatment

TCC : transitional

for bladder

cancer

cell carcinoma,

MTX : methotrexate,

VBL : vinblastine,

ADM : adriamycin

: cisplatin

Hyperthermia Hyperthermia was applied with radiofrequency (RF)-capacitive heating device (Thermotron RF-8) within 30 min after radiotherapy once or twice a week.

Heating duration was 40-50 min.

and lower electrodes were 30 cm in diameter, placed on opposite sides of urinary bladder.

Both upper The out-put

power was about 400-600W. A treatment posture of all cases was prone position. For cooling of the skin surface, the overlay boluses were applied in addition to regular boluses attached in front of the metal electrodes. The intravesical temperature was measured using a 4-point microthermocouple-sensor. The maximum intravesical temperature (Tmax)was defined as the maximum intravesical temperature obtained during the steady state and at the end of treatment. The steady state was defined at 20 min after the start of heating. The minimum intravesical temperature (Tmin) was defined as the minimum temperature obtained by the same method. The averages of these parameters (Tave) were calculated over the steady state. In all cases, Tmax,Tmin and Tave were measured at the third session. Table I summarizes the thermometry.

( 24 )

152

Regional

Hyperthermia

for

Bladder

Cancer •E

T.

Ohguri

et

al.

Radiation All

patients

radiation case

dose 1

and

3,

technique,

in

11 •~10 3,

cm2

18Gy

treated

was

66-7OGy.

the

initial

case and

2,

In

case

in

case

case

fractions

whole case

cm2

pelvic

covered

1,

1 and

in

1, 7•~7.5

external

The

covered

technique, in

with

fields

48Gy

respectively.

conformal

3,

were

2, 3, with

and

were

18•~15 fields 4-field

14Gy

2Gy

whole pelvis

the

radiotherapy

plus

using

daily,

bladder with

cm2

and

were box

regional

in to

technique,

and

linear

lymph the

case

tumor the

cm2

10MV

5 days/week

technique,

46Gy

shrunk

5.2•~5.5

given and

same

a

field

2,

field

the

size

lOGy

in

and

nodes

with and

2,

dose

8•~

X-ray

total .

In

4-field

total

and

with

total

case

1OMV

cm2

boost

A

using

size

12•~10

for

accelerator.

box

dose

4OGy

in

are case

three-dimensional are

7 cm2

7.6

and

X 8 cm2

26Gy

in

and case

respectively.

Chemotherapy Two 1,

15,

and on of

22,

of

the

29,

43

three and

doxorubicin days 70

1, mg/m2

Evaluation

patients 50,

of 15,

22, on

30 29,

day

received

vinblastine mg/m2

43

on

and

3 and

50, 43.

the of

day

following

3 mg/m2 3 and

chemotherapy on

43.

vinblastine Radiotherapy

of

days

The

15,

22,

remaining

3 mg/m2 was

3,

: methotrexate

started

on

one days

on

32,

day

43

and

50,

received

3, 3,

15, 7

22, and

of

30

mg/m2

cisplatin

of

methotrexate 32,

43

and

15,

respectively.

of 50,

and

on 70

days

mg/m2,

30

mg/m2

cisplatin

of tumor response

The clinical tumor response was evaluated by measuring the tumor size with MR imaging before and after the radiation therapy. Grading of tumor response was as follows : complete response (CR), 50 % regression in volume as partial response (PR), < 50 % response or < 25 % increase as no change (NC). Results Table II summarizes the treatment result.

CR was achieved in all the three patients.

They did not

have both local recurrence and distant metastasis. Fig. 1. shows MRI images of case 1 with bulky bladder cancer which responded completely to combined treatments. Toxicity consisted of cystitis and diarrhea noted during the treatment was acceptable and did not get serious. Acute toxicity of chemotherapy was also within the tolerance level. Severe late toxicity was not recognized in our retrospective research. Table

II

Treatment

results

NED : no evidence of disease Toxicity : criteria of radiation therapy oncology group (RTOGY")

153

( 25 )

Jpn. J. Hyperthermic Oncol. 21 (3) : 2005

日本 ハ イ パ ー サ ー ミア 誌21〔3〕:(平

Fig. la. Case 1. MR imaging (T2 weighted image) showed bulky bladder cancer (arrows).

Fig. lb. There

was no tumor

2 weeks

成17年)

after completion

of

treatment.

Discussion Radical radiation therapy as the sole treatment modality for muscle-invasive bladder cancer has produced a clinical complete response in 40 % to 50 % of patients14-16). Several authors have reported promising results of concurrent chemoradiotherapy for muscle-invasive bladder cancer17-22). Pelvic failure is less common with chemoradiotherapy than with radiation monotherapy22). For the modern bladder preservation series, TUR followed by irradiation with concurrent chemotherapy, the overall survival at 5 years ranged from 45 to 52 % ; 54 to 67 % of surviving patients have a tumor-free, normally functioning bladder1). Hyperthermia is biologically known as an effective modality for treatment of cancer.

Clinical

studies including randomized trials on hyperthermia have promising results for various sites of tumor2-12). A Dutch phase III trial showed improvement of local efficacy in a mixed cohort of patients with locally advanced cervical, bladder or rectal carcinoma, and a major survival benefit was obtained in patients with cancer of the uterine cervix by adding regional hyperthermia to standard radiation therapy12). For patients with bladder cancer, the addition of hyperthermia significantly increased the complete-response rate from 51 % to 73 % ; however, long-term local control and overall survival were not significantly improved. The value of hyperthermia in these patients might have been underestimated for various reasons as lack of thermal data analysis and the problem of patients who received insufficient hyperthermia treatment. Clinical and laboratory studies have also shown that hyperthermia enhance the cytotoxic effects of several chemotherapeutic

drug7)23)24).Kakehi et al.

showed the treatment results of RF-capacitive

regional hyperthermia with chemotherapy in patients with bladder cancer ; total response rate was obtained in 6 out of 8 cases7). Although there were a few reports of combined treatment of hyperthermia, irradiation and chemotherapy for invasive bladder carcinoma, their results were satisfactory8-10). In the combination therapy consisted of radiation and hyperthermia administered by way of warmed saline and

( 26 )

154

Regional

bleomycin

irrigation,

noted

among

T2-3

hyperthermia of

For

the

no

bladder

(>

showed

(44-47•Ž)

in

our

Although

of at

to

treat

of

the

series

patients

T.

and

Ohguri

PR

4

of

et

in

results

in

the

overlay with

a

of

al.

21,

and

an

including

the

5

84

% response

rate

RF-capacitive

patients

the

better

fat

consisted

, including

was

3

regional cases

of

T2

and

intra-vesical

RF-8. for

the

cystitis

temperature. for

three

that

tumors

with

of

tumor

the

number

of is

heating

patients

and

of

diarrhea

the

we

to

in

maximum

complete

could

obtain

bladder

temperature

tumors

average

of

excellent of

intravesical

meet

TUR

degeneration

than

higher

needs 5 cm

visibly

average

studies

session

of

with

low

intravesical

such 40-50

the

rise water06).

did

not

get

average

temperature

of

serious

and detailed

the

1 and are

fatty

could

than

in

the

potentially providing treatment

three

.

are

patients useful

for

reduced

by

, it is possible strong

cooling

despite

of

improving

therapeutic protocols

three

problems

be

by

not

Excessive

major

thick

tumor

are

probably

often

3 cm

deep-seated

2,

sufficient

layer

edge less

treatments

case

minutes

fat

seems

cancer with

as

electrode

subcutaneous

of

hyperthermia

subcutaneous

hyperthermia bladder

Further

and 5 cm,

high

of

near with

point

Regional

than

histological

obtained,

duration

a temperature

freezing

in

that

less

bladder

degeneration

believe

overheating

obtain

preservation

size

exceeded

reported

We

the

patients

Thermoesthesia

muscle-invasive protocols.

tumor

temperature

slender and

unifocal, of

bladder

response. and

and

with of

local

method

electrodes

outputs

bladder-preservation

al.

for

capacity

our

41.5•Ž25).

with

RF

results

good of

candidate

are

influence

treatment

As

intravesical

are

good

bolus.

subcutaneous

treatment

to

using

more

ideal

that

et

than

heating if

edge

the

size

higher less

led

hyperthermia

Toxicity

cases

Cancer •E

treatment

tumors

Nishimura

of

hyperthermia

higher

56

obtained

cancer,

tumor

significantly

strictly,

an

Bladder

thermoradiotherapy,

optimal

established

using

of

obstruction,

survival.

temperature

deep

25

was

T2-3a

ureteral

preoperative

intravesical

for

combined CR

Although

and

41.5•Ž)

heating

The

bladder

of

tumor1).

after

sessions

in

: primary

presence

control

cancer

observed

reported

muscle-invasive criteria

diameter,

local

also

for

T48).

following

the

was

cases10).

were

2 cases

the

CR

Hyperthermia

the the

flexibility in

large

in

number

of

recommended.

References 1) Gunderson L. L., Tepper J. E. : Bladder cancer : clinical radiation oncology, Churchill Livingstone, pp819-843, 2000. 2) Abe M., Hiranka M. Takahashi M., Egawa S., Matsuda C., Onoyama Y., Morita K., Kakehi M., Sugahara T. : Multi-institutional studies on hyperthermia using an 8-MHz radiofrequency capacitive heating device (Thermotron RF-8) in combination with radiation for cancer therapy. Cancer, 58 : 1589-1595, 1986. 3) Terashima H., Nakata H., Yamashita S., Imada H., Tsuchiya T., Kunugita N. : Pancoast tumour treated with combined radiotherapy and hyperthermia-a preliminary study. Int J Hyperthermia, 7 : 417-424, 1991. 4) Lee C. K., Song C. W., Rhee J. G., Foy J. A., Levitt S. H. : Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy : results of a phase I/II study . Int J Radiat Oncol Biol Phys, 32 : 733-745, 1995. 5) Imada H., Nomoto S., Tomimatsu A., Kosaka K., Kusano S., Ostapenko V. V., Terashima H. : Local control of nonsmall cell lung cancer by radiotherapy combined with high power hyperthermia using an 8 MHz RF capacitive heating device. Jpn J Hyperthermic Oncol, 15 : 15-19, 1999. 6) Ohguri T., Imada H., Yahara K., Kakeda S., Tomimatsu A., Kato F., Nomoto S., Terashima H., Korogi Y . : Effect of

155

( 27 )

Jpn. J. Hyperthermic Oncol. 21 (3) : 2005

8-MHz radiofrequency-capacitive colorectal

regional hyperthermia

cancer. Int J Hyperthermia,

7) Kakehi M., Ueda K., Mukojima studies on hyperthermia J Hyperthermia, 8) Ueda

radiofrequency

with strong superficial cooling for unresectable

成17年)

or recurrent

20 : 465-475, 2004.

T., Hiraoka

M., Seto 0., Akanuma

combined with radiotherapy

A., Nakatsugawa

or chemotherapy

S. : Multi-institutional

clinical

in advanced cancer of deep-seated organs. Int

6 : 719-740, 1990.

K., Sakagami

H., Kato

hyperthermia,

invasive bladder 9) Noguchi

日本 ハ イ パ ー サ ー ミア 誌21〔3〕:(平

F., Mogami

T., Ohtaguro

HPC-adriamycin,

carcinoma. Nippon

K., Masui Y. : A combined

immunotherapy,

Hinyokika

radiation,

local hyperthermia

for bladder cancer. Nippon

systemic chemotherapy

Hinyokika

therapy of intra-arterial

and irradiation

for

chemotherapy

and

Gakkai Zasshi. 81 : 1817-1824, 1990. (Japanese).

S., Watai K., Kakehi M., Kubota Y., Yao M., Shuin T. : Combination

bladder carcinoma with chemohyperthermia.

with 8 MHz

Gakkai Zasshi. 81 : 1330-1336, 1990. (Japanese).

R., Sasaki A., Miyanaga N., Kanoh S., Koiso K. : Combination

10) Matsui K., Takebayashi

treatment

Int J Hyperthermia.

radiotherapy

of urinary

7 : 19-26, 1991.

11) Colombo R., Da Pozzo L. F., Lev A., Salonia A., Rigatti P., Leib Z., Servadio C., Caldarera E., Pavone-Macaluso Local microwave hyperthermia

and intravesical

unresectable

tumors. J Urol, 159 : 783-787, 1998.

superficial bladder

chemotherapy

as bladder

M. :

sparing treatment for select multifocal

and

12) van der Zee J., Gonzalez Gonzalez D., van Rhoon G. C., van Dijk J. D., van Putten W. L., Hart A. A. : Comparison of radiotherapy randomised,

alone with radiotherapy

multicentre

plus hyperthermia

trial. Dutch Deep Hyperthermia

in locally

advanced

pelvic tumours : a prospective,

Group. Lancet, 355 : 1119-1125, 2000.

13) Cox J. D., Stetz J., Pajak T. F. : Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization 14) Jahnson

for Research and Treatment

of Cancer (EORTC).

S., Pedersen J., Westman G. : Bladder carcinoma--a

Int J Radiat Oncol Biol Phys, 31 : 1341-1346, 1995.

20-year review of radical irradiation

therapy. Radiother

Oncol, 22 : 111-117, 1991. 15) Bloom

H. J., Hendry

pre-operative 16) Mameghan transitional

W. F., Wallace

radiotherapy

of

Br J Urol, 54 : 136-151, 1982. for invasive

radiation

and cisplatin in the treatment of advanced

report. J Urol, 128 : 1031-1033, 1982.

T4_,Zur Nedden D. : Combined radiation

of the urinary bladder.

and chemotherapy

for locally advanced transitional

Cancer, 55 : 1659-1664, 1983.

19) Shipley W. U., Prout G. R. Jr., Einstein A. B., Coombs L. J., Wajsman Z., Soloway M. S., et al. bladder cancer by cisplatin and radiation 20) Tester W., Poter A., Asbell S., Coughlin organ preservation

trial

of the bladder. Int J Radiat Oncol Biol Phys, 31 : 247-254, 1995.

bladder cancer : a preliminary

cell carcinoma

cancer : controlled

J., Brook S. : Analysis of failure following definitive radiotherapy

17) Soloway M. S., Ikard M., Sceinberg M., Evans J. : Concurrent

18) Jakse G., Frommhnld

of T3 bladder

and radical cystectomy versus radical radiotherapy.

H., Fisher R., Mameghan cell carcinoma

D. M., Skeet R. G. : Treatment

Treatment of invasive

in patients unsuited for surgery. J Am Med Assoc, 258 : 931, 1987. C., Heaney J., Krall J., et al. : Combined

modality

program with possible

for invasive bladder carcinoma : results of RTOG protocol 85-12. Int J Radiat Oncol Biol Phys, 25 :

783-790, 1993. 21) Dunst J., Sauer R., Schrott K. M., Kuhn

R., Wittekind

C., Altendorf-Hoffman

A. : Organ-sparing

treatment

of

advanced bladder cancer : 10-year experience. Int J Radiat Oncol Biol Phys, 30 : 261-266, 1994. 22) Coppin C. M. L., Gospodarowicz

M. K., James K., Tannock

I. F., Zee B., Carson J., et al. : Improved local control of

invasive bladder cancer by concurrent cisplatin and preoperative

or definitive radiation.

J Clin Oncol, 14 : 2901-2907,

1996. 23) Kawai H., Minamiya doxorubicin

Y., Kitamura

concentration

M., Matsuzaki

I., Hashimoto

M., Suzuki H., Abo S. : Direct measurement

in the intact, living single cancer cell during hyperthermia.

24) Schopman E. M., Van Bree C., Kipp J. B. Barendsen G. W. : Enhancement treatment of solid tumours by application

( 28 )

of local hyperthermia.

156

Cancer, 15 : 214-219, 1997.

of the effectiveness of methotrexate

Int J Hyperthermia,

of

11 : 561-573, 1995.

for the

Regional

25) Nishimura

Y., Hiraoka

J Hyperthermic

Hyperthermia

M. : Relationship

for

Bladder

Cancer •E

T.

Ohguri

et

al.

between thermometry results and tumor response in thermoradiotherapy.

Jpn

Oncol, 14 : 162-169, 1998.

157

( 29 )

Jpn. J. Hyperthermic Oncol. 21 (3) : 2005

日本 ハ イ パ ー サ ー ミア 誌21〔3〕:(平

成17年)

浸潤性膀胱癌 に対 す る温熱化学放射 線治療 による 膀胱温存療法 の初期経験 大 栗 隆 行 ・今 田   肇 ・野 元   諭 ・加 藤 文 雄 矢 原 勝 哉 ・森 岡 丈 明 ・中 野 敬 太 ・興 梠 征 典 産業医科大学放射線科学教室



旨: 近 年,浸 潤 性 膀 胱 癌 に対 して経 尿 道 的 腫瘍 切 除,放 射線 治療 と化 学 療 法 の併 用 に よ る膀 胱 温

存 を 目的 と した 治 療 が施 行 され,膀 胱全 摘 除 術 に 匹敵 す る成 績 が報 告 され て い る.我 々 は,3例 の腫 瘍 径 の大 きな浸 潤 性 膀 胱 癌 に対 し,局所 効 果 の増感 を 目的 に,化 学 放 射線 治療 に温 熱 療 法 を加 えた膀 胱 温 存 療 法 を施 行 した.病 期 はT2N 分割 で66-70Gy,温

lMO(2例),

熱 療 法 を3-12回,ま

T2NOMO(1例),平 たM-VACを

均 腫瘍 径 は5.7cmで

あ った.放 射 線 治 療 は通 常

主体 とした化 学 療 法 を施 行 した.治 療 後,全3例



も腫瘍 は完 全 消 失 し,局 所 再 発 や 遠 隔 転移 を生 じなか った.治 療 期 間 中 に膀 胱炎 や下 痢 を生 じた が,治 療 終 了後 改善 し,重篤 な晩 期 障害 も認 め られ なか った.腫 瘍 径 の大 きな浸潤 性 膀 胱 癌 に対 す る化 学 放 射 線 治 療 に温 熱療 法 を加 えた 膀 胱 温存 療 法 は有 用 で 治療 成績 の改 善 が 期 待 で き る.

( 30 )

158