The place of radiotherapy in the treatment of synovial sarcoma

Inr J Rodmmn Onmlo~ lliol. Phyr.. Vol Rmtcd in the U.S.A. All rlghtr rncrved

03~3016/81/0100)eOsu)2.00/0 Copyright 0 1981 Pergamon Press Ltd.

7. pp. 49-53

??Original Contribution THE PLACE OF RADIOTHERAPY IN THE TREATMENT OF SYNOVIAL SARCOMA JOHN H. CARSON,

Bsc., M.D.,* ANDREW R. HARWOOD, M.B., F.R.C.P.(C),t M.B., F.R.C.P.(C),t VICTOR FORNASIER, M.D., F.R.C.P.(C),$ FREDERICK LANGER, M.D., F.R.C.S.** AND IAN QUIRT, M.D., F,R.C.P.?‘F

BERNARD J. CUMMINGS,

Princbs Margaret Hospital. Toronto, Ontario, Canada Tltispaperreviews 36 patientswitbsyaovialsarcotna;18 were referred within three months of surgery. None had undergone“en bloc” excision and aJI were treated with post-operative radiotherapy. Local control and survival were narlyzed with respect to Tumor Node Metastasis Classification, htioiogy, site of primery and surgical pro&ure. Eit patients with TI-ZNOMO tumors were alive and wdl (minimum two year follow-up) following excision and is alive ndiiherapy; 7 had a normally functional extremity. IA contrast, only one of 8 prtients with T3N8MOtumors

andwell.!5even of 8 patients withwellor t&erately differtntiated biology werealive&

wellwhereas M)patient

witb poorly d@renGated hitologies survived. Six of 7 patients were alive aml well if their tumor was distal to the

elboworkaeewbereasroseoftbasewhobadaprimuytbigbs~~ wrvived.Eigben ptimts wm ~~ni~bneMcnt~~2mnulryled.A~~Bdicyisproparcdforr~lsucaarnidbtLe integrated @seof wrgery,radiitioaandcbemother8py; it eizes optimalcureratesti 8 femctimd exbeaity reserving amputation for salvqe. Synovial sarcoma, Radio-y.

INTRODUCTION

between January, 1958 and December 31. 1977. We divided the patients into two separate groups; those who were referred within three months of biopsy or surgery were classified as primary cases and all others were classified as recurrent either locally, regionally (in the lymph nodes) or with distant metastases. The patients were staged retrospectively according to the Union Internationale Contre le Cancer (UICC) Tumor, Node, Metastases Grade (TNMG) Classification (Table I).” This differs slightly from the American Joint Committee staging system in which all synovial sarcomas are classified as Stage 3.9 Local excision is defined as a local removal of the tumor alone without any attempt to remove a wide rim of normal tissue around the tumor as is carried out in an “en bloc” wide local excision. We classified all such patients as having probable microscopic residual disease. In some patients local excision was attempted and gross residual tumor was left behind; these have been classified as macroscopically incomplete. Review of pathology in our institute was carried out in 12 of 16 primary cases by one

Synovial sarcoma comprises 7% of all soft tissue sarcomas and occurs chiefly in the extremities.’ The traditional treatment of this disease has been either amputation or local excision.“4q6 There have been only a few reports on the use of irradiation therapy alone or in conjunction with excision.‘*‘.‘.* Amputation for this disease produces a major functional deficit and local excision is commonly associated with local recurrence rates of 30-70%; “en bloc” wide local excision frequently is impossible to carry out because of a propensity for the tumor to occur in the hand, foot and knee regions. The purpose of this report is to review the experience of the Princess Margaret Hospital using radiation therapy to treat patients with this disease and to define the relative roles of conservative or ablative surgery, irradiation and chemotherapy. METHODS AND MATERIALS All case histories were reviewed for patients with biopsy proven synovial sarcoma during a 20 year period *Resident in Radiation Oncology, Department of Radiation Oncology. tRadiation Oncologist, Department of Radiation Oncology. SPathologist, Department of Pathology. **Consultant Surgeon. ttMedical Oncologist, Department of Medicine.

From the Sarcoma Group, The Princess Margaret Hospital. Reprint requests to: Dr. A.R. Harwood, Princess Margaret Hospital, 500 Sherbourne St., Toronto, Ontario, Canada, M4X

1K9.

Accepted for publication 27 August 1980.

49

50

Radiation Oncology ??Biology ??Physics

Table 1. Staging system of synovial sarcoma

Tl

Less than 5 cm in size

T2 T3

Lesion 5 cm or greater in size Lesion of any size but grossly invading bone, major

blood vessel or nerve NO No regional lymph nodes N 1 Regional lymph node metastases MO No distant metastases M 1 Clinical evidence of distant metastases G I Low grade synovial sarcoma G2 Moderate grade synovial sarcoma G3 High grade synovial sarcoma Gx Not graded

of us (VF); in the other 4 there was no doubt about the histology of the tumor but the degree of differentiation could not be determined. The detailed criteria for inclusion is a G I, G2 or G3 stage is given elsewhere.9 Thirty-six patients with synovial sarcoma were seen during this period. There were 26 males and 10 females; their ages ranged from 6-72 years with a median age of 35 years. Eighteen cases were primary and 18 cases were recurrent. In 16 of the 18 patients with primary tumors, the tumor was confined to the original site (Table 2). Two of these patients had regional lymph node metastases (an incidence of I 1%) and both died of their tumor. For those patients who received a tumor dose of approximately 5000 rad, there was a reduction in the size of the field at 3500 rad to spare limb circumference, if possible. Those treated with a O-7-21 day, or hypoxia tourniquet technique did not have an alteration of the field size. RESULTS Table 3 analyzes the survival of the patients with primary tumors versus TNM stage, all patients with stage Tl and T2NOMO were alive and well for periods ranging from 2-14 years following treatment, whereas only t of IO of the T3NOMO or Tl-3Nl MO staged patients was alive and well. Table 4 analyzes the outcome of the 16 patients with primary tumor and without nodal disease versus degree of differentiation of the tumor. Seven of 8 patients with well and moderately differentiated tumor were alive and well. The only death was a patient with a T3 tumor of the groin and thigh. In contrast, none of the patients with poorly differentiated tumors were cured of their tumor. Four patients who were classified as Gx could not be graded because the original slides had been discarded and the pathology report did not specifically mention grade. In I I patients, disease was of biphasic variety: it was of the monophasic variety of the epitheliod type in four patients and probably of a biphasic variety in one. Table 5 analyzes the outcome of the 16 patients with primary disease and without nodal disease versus site. Patients with tumors distal to the knee or elbow did well (6 of 7 alive) whereas those with provimal tumors particularly of the thigh and buttock did poorly (0 of 5 alive).

January I98 1, Volume 7, Number 1

Tables 3, 4 and 5 show that there is a close interrelationship between stage, differentiation and site versus outcome. Patients with well differentiated tumors of the peripheral extremity did well and those with extensive poorly differentiated tumors of the thigh and buttock did poorly. Table 6 shows the outcome of the 16 patients with primary tumors and without nodal disease according to adequacy of surgery. None of the 16 patients had an adequate “en bloc” wide local excision. Local control was 100% in the 7 patients who had only microscopic residual disease left behind after surgery operative radiotherapy.

and who received

post-

Two patients with gross residual disease after surgery but with Tl or T2 tumors were controlled locally (one alive and well at three years, one dead of intercurrent disease at I3 years) with the use of post-operative radiotherapy. In contrast, only 2 of 8 patients with T3 tumors (one of the two dead of distant me&stases) had local control after the addition of post-operative radiotherapy when only a biopsy was done or when gross residual disease was left behind. Eighteen patients were referred with recurrent or metastatic tumor following primary surgical management carried out elsewhere. The primary sites were knee in 9; thigh, groin, and pelvis in 4; foot in 2; and hand in 3. Surgical treatment had been local excision in 9 and amputation in 8. The site of recurrence was local in 7 and distant in II patients. Two of the 7 had local recurrences salvaged by amputation (I patient) and radiotherapy (I patient). The time to first recurrence was less than one year in IO patients, l-3 years in 4, 3-10 years in 3 and greater than 10 years in I. DISCUSSION The optimal management of synovial sarcoma remains to be determined. Some advocate radical removal including amputation without further treatment,3.4.6 others advise less radical surgery combined with irradiation therapy and chemotherapy with the objective of producing survival similar to that after amputation while preserving a useful extremity.‘.z.5*7 In recent years there has been an increasing trend toward reserving amputation for recurrences after excision and irradiation therapy. A prospective clinical trial in soft tissue sarcomas is currently underway in which patients are randomized between amputation versus limited resection and radiotherapy. All patients subsequently receive chemotherapy with or without immunotherapy.’ To date no difference in number of recurrences has been seen between the two treatment arms. Our results and those of others using excision combined with post-operative radiotherapy support this management policy in patients with synovial sarcoma.‘.‘.’ Patients with Tl or T2 tumors have done well after excision combined with post-operative radiotherapy particularly if the tumors are well or moderately differentiated and are at the elbow or knee and below; all but one

51

Synovial sarwma treated with radiotherapy. J.H. CARSON er al. had a functional extremity contrast. which

patients

at the time of this writing.

with

are advanced

poorly

(T3)

differentiated

excision where feasible. The reason why we have a larger

In

proportion of well or moderately

tumors

differentiated

synovial

sarcomas compared to other series is unclear but proba-

and occur in the thigh and

patients are cured of their tumor.6 In this grouping of

bly is a result of chance or selection of patients prior to referral. A problem in advising wide local excision combined with post-operative radiotherapy in synovial

tumors

sarcomas

buttock have done poorly. However,

even

with

amputation,

very

it is recognized that few of these particular

a more aggressive treatment program is indicated

with combined chemotherapy,

irradiation

is that

wide

“en

bloc”

excision

frequently

cannot be accomplished because of its propensity to occur

and wide local

Table 2. Primary synovial sarcomas Surgery Patient

Site

Stage

Macroscopic

Microscopic

Irradiation Radffractionsfweeks (field size-cm)

Tl NOMOGl

Local excision complete

Incomplete

4500/20/4 (10x6)

TINOMOGI

Local excision complete

incomplete

2400/3/3 (10x45)

Elbow

TINOMOGI

Local excision complete

Incomplete

5000/24/5

4.

Elbow

TI NOMOGx

Local excision incomplete

Incomplete tumor spill

2400/3/3 (10x45)

5.

Wrist

TINOMOGZ

Local excision incomplete

6.

Groin

Tl NOMOGZ

Local excision complete

incomplete

5500/24/5 (16x32)

I.

Groin

TZNOMOG 1

Local excision complete

Incomplete tumor spill

4500/31/6 (variable)

8.

Knee

TZNOMOG 1

Local excision complete

Incomplete

l2.000/12/12 (20x60)

9.

Upper arm

T3NOMOG3

Incomplete

Incomplete

8250/3/3 (15x20)

10.

Ankle

‘T3NOMOGx

Local excision incomplete

11.

Thigh

T3NOMOG3

Incomplete

12.

Groin and thigh

T3NOMOG 1

Local excision incomplete tumor spill

13.

Buttock

T3NOMOG3

Incomplete

14.

Parotid

T3NOMOGx

Local excision incomplete

4000/15/3 (10x28) 2400/3/3 (6x 12)

15.

Thigh

T3NOMOGx

Local excision incomplete

82501316 (19x16)

16.

Thigh

T3 NOMOG3

Local excision complete

I.

Elbow

2.

Hand

3.

’

SOOO/lO/2 (6x 12)

4500/20/4 (15x62) incomplete

5160/32/l (20x42) 3500/3/21 (12x20)

Incomplete

Incomplete

2400/3/3 (20x60)

Results Alive and well 10 years. Normal limb function. Alive and well 4 years. Normal limb function. Alive and well 5 years. Normal limb function. Alive and well 3 years. Normal limb function. Dead heart attack 13 yrs. no recurrence to death, Normal limb function. Alive and well 2 yrs. Normal limb function. Alive and well 6 yrs. Normal limb function. Alive and well 14 yrs. Poor limb function. Primary controlled Dead lung mets. 6 months. Alive and well 6 years. Normal limb function. Dead of local recurrence and distant mets. 6 months. Dead of local recurrence and distant mets. in 6 months. Dead local recurrence 2 years. Dead of local recurrence and distant mets. I year Dead edge recurrence of primary 6 months. Primary controlled dead lung mets. 1 year.

52

RadiationOncology0 Biology 0 Physics by TNM

Table 3. Redts

January I98 I. Volume 7, Number 1

stage (primary synoviai sarcoma)

TN M stage*

Table 5. Results by primary site (primary synovial sarcoma): No. natients onlv

Status (alive and well) Primary site

TINOMO TZNOMO T3NOMO

616 2/2 l/8 (2 dead primary recurrences 5 dead distant metastases) Of2

Tl-3NlMO

Status (alive and well)

Peripheral extremity (elbow or below, knee or below) Thigh and buttock

617 015

*Tumor, node, metastasis. ment in which the tumor in the region of the knee, wrist and ankle joint. indicates G2,

that if the tumor

a complete

resection

though the tumor compatible documented which

is not

a functional

extremity.

in the literature

of post-operative

with local recurrence not adequate

tive radiotherapy confirms

the

that

when

patients

with

be given

recurrences

plus or minus radiotherapy that amputation

salvage

of recurrence

treatment. therapy prefer

to treat

operative tumor

control

in patients

following

sole or achilles therapy

adjuvant

that

It is our

against

function

with

region.

We

and postthat

local

tumors.

combination

of tumor,

a

in the T3 stage groupparticularly

Evidence

those

with

is accumulating

chemotherapy

may

be of

analysis

illustrates

of our .patients

that the majority

three years of primary patient

with

recurrent

of recurrences

treatment

disease

occur within

but that the occasional

may recur many years after

This emphasizes

with

hypoxic

technique

initial

the need for continued

management.

follow-up

very

high

of the extremity

One patient

in our series was

doses of irradiation

and had very poor limb of irradiation

in these

patients. For post-operative radiation therapy, we currently use doses of 5.000 rad in 3 weeks in 20 fractions. The full and the whole muscle compart-

Gl orG2 G3 Gx

Status

(alive and well)

7/Y (1 death III T3 tumor) (J/-I (all T3 tumors) I /4 (3 deaths in T3 tumors)

function

as a

It is difficult to be dogmatic about the optimal management of a rare tumor such as synovial sarcoma. However,

on the basis of this review,

cure rate combined

with

the current

group emphasizes

preservation

Tl

managean optimal

of function

or TZNOMO.

Gl

or G2. “peripheral

of the

sites.” Wide

local excision

(if possible)

plus routine

post-operative

radiotherapy.

If wide local “en bloc” excision

cannot

be done because of location, then the bulk of tumor compatible with a functional extremity should be or

and radiotherapy TZNOMO.

Management

G3

should be given. tumors

as in I) but with

vant chemotherapy tine. doxorubicin (CYVADIC). Al1 T3 tumors

or

plus any tumor

pre-operative

post-operative

sites. of adju-

with nodal involvement.

chemotherapy

apy plus wide local “en bloc” excision plus

proximal

the addition

using cyclophosphamide, vincrisand imidazole carboxamide

adjuvant

and radiother(where

possible)

chemotherapy

for

six

IO patients

with syno-

months. We have treated

vial sarcoma

approximately

using this protocol

since January

1978 but

these patients

in this study.

Table 6. Results by adequacy of surgery (primary synovial sarcoma): No. patients only Status

Table 4. Results by degree of differentiation (primary synovial sarcoma): No. patients only TN M stage

the

has now been aban-

follow- up time is too short for us to include

thickness of the extremity

using

doned.

Combined

benefit in this situation.’ The

of 5 cm proximal

to spare part of the thickness

treated

Tl

in these sites.

metastases.

attempt

a margin

scar. Where possible, we always

from this booster treatment..

removed

can be preserved

of local control

to 3,500 rad;

extremity:

radiation

tendon

was excised with

ment policy of our sarcoma

excision

associated

by local excision

of patients

ditferentiated

local

as we have found

to the problem

proportion

study

showed

the tumor

and distal to the surgical

result. This technique

should be reserved for attempted

and useful limb

ing die of distant poorly

which

or complications

with tumors

In addition significant

Our

can still be salvaged.

such patients

radiation

by

or higher.5 This is

rr al.’ have advised

Suit

to the foot,

excision,

it is associated

routinely.

al. study’

et

opinion

local

for this disease and post-opera-

should

local

has been

is not followed

rates of 35-70s

Shui

essential

It

radiotherapy,

treatment

G 1 or

if this is feasible and

is not an “en bloc” resection,

addition

that

absolutely

should be removed

with

Our study

is stage Tl or TZNOMO.

arises is irradiated

then a booster dose of 1,500 rad is given to the area where

Biopsy only Gross residual tumor post surgery tumors) Microscopic residual tumor

(local control)

I /3 (all 3 patients died of tumor) 3/6 (all 3 local failures in T3

717

Synovial sarcoma treated with radiotherapy 0 J.H. CARSONet al.

53

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1963. 2. Cadman N.K., Soule E.H., Kelly P.J.: Synovial sarcoma. An analysis of 134 tumors. Cuncer 18: 613-627, 1965. 3. Cameron H.U., Kostuik J.P.: synovial sarcoma. J. Bone Joint 4. Hajdu S.I., Shui M.N., Fortner ma. A clinicopathologic study 1201-1217, 1977. 5. Murray J.A.: Synovial sarcoma.

A long term

follow-up

of

Swg. 56B: 613-6 17, 1974. J.G.: Tendosynovial sarcoof 136 cases. Cuncer 39:

Orth. C/in. North Am. 8:

963-972, 1977. 6. Shui M.H.,

McCormack P.M., Hajdu S.I.. Fortner J.G.: Surgical treatment of tendosynovial sarcoma. Cuncer 43: 889-897. 1979. 7. Suit H.D.. Russell W.O., Martin R.G. Sarcoma of soft

tissue. Clinical and histopathologic parameters and response to treatment. Cancer 35: 1478-1483, 1975. 8. Rosenberg S.A., Kent H., Costa J., Webber B.L., Young R., Chabner B., Baker A.R., Brennan M.F., Chretien P.B., Cohen M.H.. DeMoss E.V., Sears H.F., Seipp C., Simon R.: Prospective randomized evaluation of the role of limb sparing surgery, radiation therapy and adjuvant chemoimmunotherapy in the treatment of adult soft tissue sarcomas. Surgery 84: 62-68, 1978. 9. Russel W.O.. Cohen J., Enzinger, F. Hajdu, S., Heise, H., Martin, R., Meissner, W., Miller W.T., Schmitz R.L., Suit, H.D.: A clinical and pathological staging system for soft tissue sarcomas. Cancer 40: 1562-l 570, 1977. IO. international Union Against Cancer (UICC): TNA4 Clossijcution ofbfulignunr Tumors. Geneva, UICC. 1974. pp.

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