RADIATION THERAPY I N THE PALLIATIVE MANAGEMENT OF SOFT TISSUE SARCOMAS

HAROLD PERRY, M.D.,” AND FLORENCE c. H. CHU, M.D.

OFT TISSUE SARCOMAS are relatively uncom- S mon. The management of this group of sarcomas has been primarily surgical.1-* Al- though radiation therapy has been used pre- operatively, postoperatively, and for the treat- ment of recurrent, residual, or metastatic disease, its efficacy has not been fully assessed. I t is the purpose of this paper to discuss the role of ionizing radiation in the palliative management of these neoplasms.

Between Jan. 1, 1949, and Dec. 31, 1959, 104 patients with soft tissue sarcomas were treated in the Department of Radiation Ther- apy of Memorial Hospital for Cancer and Al- lied Diseases, New York, N.Y. In all cases reported here there was a positive histological diagnosis. When possible, all available slides made from biopsy, operative, and/or autopsy material were reviewed by the Department of Pathology of the hospital. The term “spindle cell sarcoma” was applied to those cases in which the histological findings did not permit further classification.

The distribution of the 104 cases according to histological type was as follows: liposar- coma, 29; rhabdomyosarcoma, 36; leiomyosar- coma, 5 ; synovial sarcoma, 12; fibrosarcoma, 7; and spindle cell sarcoma, 15.

The liposarcoma group was composed of 2 subgroups: 24 cases of liposarcoma and 5 cases

From the Department of Radiation Therapy, Me- morial Hospital for Cancer and Allied Diseases, 444 E. 68th St., New York 21, N.Y.

Presented in part at the 7th International Cancer Congress, July, 1958, London, England.

We are grateful to Dr. Ralph F. Phillips and Dr. James J. Nickson of the Department of Radiation Therapy, Memorial Hospital for Cancer and ,411ied Diseases, for their many suggestions and €or the use of their clinical material. We wish to thank Dr. A. S. Glicksman for his invaluable assistance in the prepara- tion of this paper. We are indebted to Dr. Frank W. Foote and Dr. J. Budinger of the Department of Pa- thology, Memorial Hospital for Cancer and Allied Diseases, for their review of the material in the cases reported here. Our sincere thanks also extend to Mr. G. Bahr and Mr. C. Herbert of Cincinnati General Hospital, Cincinnati, Ohio, for their assistance in the statistical evaluation of the data.

* Present address: Department of Radiology, Cincin- nati General Hospital, 3231 Bumet Ave., Cincinnati 29, Ohio.

Received for publication March 6, 1%1.

of myxoliposarcoma. There were also 2 sub- groups in rhabdomyosarcoma: 23 cases of the embryonal type and 13 cases of the adult type.

TREATMENT

In the 104 patients with soft tissue sar- comas, 227 courses of radiation therapy were administered. The great majority of these treatments were to the recurrent or metastatic tumors for palliation. Treatment techniques were varied to suit the clinical situation pre- sented by each patient and depended upon the history of prior treatment, the general condition of the patient, and the site and size of the neoplasm. Most patients were treated with radiation alone. In some instances, com- bined radiation and chemotherapy or radia- tion and limited surgery were utilized in an effort to achieve the maximum palliation. Many kinds of therapeutic equipment were used in the treatment of this series of patients. Included were superficial, high, super, and megavoltage X rays, telecobalt, and megavolt- age electron beams. Also, radioactive sources were used in a few cases in which interstitial implantation appeared to provide optimal treatment. All dosages are expressed here as tumor dose.

RESULTS

When possible, the results of treatment were evaluated both objectively and subjectively. An objective response was a measurable de- crease in size or disappearance of the lesion under treatment. A subjective response was amelioration of relevant symptoms present prior to the first treatment. Duration of ob- jective response was scored from the time of the first sign of regression of the lesion to the time when measured values increased again. Duration of subjective response was scored from the time when relevant symptoms were stated to decrease to the time when there was a return of a given symptom or symptom com- plex. Survival data will not be presented in this report since in the majority of cases radia-

179

180 CANCER January-February 1962 Vol. 15

'FABLE 1 O\.'ER-ALI, RESIJL'TS OF RADIATION 'TIIEATMENT I N

I'ATIENTS WITH SOFT TISSUE SARCOMAS ~~ .__ _____ - ~ . _ _ _ . . _ ~ _ _ _ _ _ _ _ _ I ___

N o responsc Response AV. durat. ~- _. .- - _ ~ Group KO.

Type courses No. 5% No. % response, sarc. treat. courses courses courses courses mo.

1 1.i pos;rrc. 87 12 1.3.8 7 5 86.2 11.G

, . -. -.

Liposarc. 74 9 12.2 6 5 87.8 10.7 M ysoliposirc. 13 3 23. 10 77. 16.3 -

Rhabdomyosarc. Etiibrytrnal Adirlt

> l,eic.)myos;irc. 4 Synovial mrc. 5 Fibrosnrc. 6 SpintIlc cell sm.

'ro,r,u,

59 41 18

12

30

16

2 3

227 -_ -

18 30.5 10 24.4 31 8 43.5 10

5 41.7

9 30.

5 31.3

10 43.5

5 9 26.

41 69.5 6 . 1 75.6 3.8 55.5 12.3

7 58.3 4 . 0

21 70. 6 . 8

11 68.7 4.4

13 56.5 4.7

168 74. 8 . 4 -

tion therapy was instituted as a palliative measure and as only a part of the over-all plan of I reatment.

'l'he oicr-all results o f treatment are prc- serited in Table 1. Of the 227 courses of radia- tion given to various types of sarcomas, 168 ( 7 4 3 produced objective response. In the majority of instances (all save 26) the tlura- I iori of response could be determined, and the ;tvci age duration of regression was 8.4 months.

Amelioration of symptoms was obtained in all instances in which objective regression oc- ciiried. A s a rule, the duration of subjective response closely paralleled the duration of o b j e c t i w response in this group of patients.

Croirp 1. Lil)osarconia. Twenty-nine pa-

TARLE 2 'I'IUUOR RESPONSE: IN RELATION TO

ItADI,\TION DOSE USED IN TREATING I'.\'TIlSN'I'S WITH LIPOSARCX3MXS

' l ' 0 t ~ 1 No resp., liesp., r m , 1 1 0 . 110. 110. r courses cowses* courses*

~

100-500 3 2 1 501-1,000 12 2 10

1,00 1-1,500 8 2 (myxo.) 6 1,501-2,000 14 2 12 (1 ntyxo.) 2,001-2,500 17 2 15 2,501-3,000 14 2 ( I myxo.) 12 ( 2 myxo.) 3,001 -3,500 9 0 9 3,501 -4,000 3 0 3 (2 myxo.) 4,001-4,500 4 0 4 (1 myxo.) 4,501 -5,000 1 0 1 (myxo.) 5,oo 1-5,500 1 0 1 (myxo.) >5,500 1 0 1

_. _. _ _ 75 (86.2) r .

l 0 T A L 87 1 2 ( 1 3 8 ) ~ ____-____ ~

*The figures in parentheses are percentages.

tients received 87 courses of treatment for palliation (Table 1). Twcn ty-four cases were diagnosed as liposarcoma, and these patients receivecl 74 roiirses of treatment. Five cases were diagnosed as niyxoliposarc oma arid this group received 13 courses of treatment.

I n the liposarcoma group, the i a n p of tu- mor close was from 200 r in 1 day to 6,100 r in 51 days. Objective response was obtaincd i n 65 courses oC tieatment (87.87"). T h e tlura- tion of response was known in all but 3 in- stances. T h e avcrage duration was 10.7 months, with a range of 2 to 28 months. The radiation dose delivered and the response oE the lesions were correlated and arc presented in Table 2. There was a high re\ponse rate to a tumor dose as low as 1,000 r. No patient failed to respond to irradiation when a dose of 3,000 r or more was given.

In the myxoliposarcoma group, the range of tumor dose was from 100 r in 4 (clays to 5,300 r in 43 tlajs. Ten of the I S courses o f treatment produced favorable results. T h e average duration of response was 16.3 months, with a range of 2 to 79 months. A regression of 79 months' duration was obtained in a pa- tient with residual pelvic tumor. No tumor was found on sub\equent abdominal explora- tion. From Table 2 it can be seen that the 3 treatment failures occurred in paticnts re- ceiving 3,000 r or less.

Jn the total 'group of patients with lipo- sarcoma and myxoliposarcoma, thc response rate was 86.271,, and the average cluration oE response was 11.6 months. An attempt was

No. 1 RADIATION PALLIATION OF SOFT TISSUE SARCOMAS Perry & Chu 181

made to correlate the duration of regression TABLE 4 with the doses delivered, but no disiernible pattern was observed.

Group 2. Rhabdomyosarcoma. Thirty-six patients received 59 courses of treatment (Ta- ble 1). Twenty-three patients had a diagnosis of embryonal rhabdomyosarcoma and received 41 courses of treatment. Thirteen cases were diagnosed as rhabdomyosarcoma, adult type, and these patients received 18 courses of radia- tion therapy.

In the embryonal rhabdomyosarcoma group, the age of the patients vaned from 20 months to 17 years. Forty-one courses of radiation therapy were administered, 15 of which were combined with chemotherapeutic agents, such as actinomycin D, nitrogen mustard, 6-mer- captopurine, and amethopterin. The dose range was 500 r in 5 days to 4,800 r in 30 days. Thirty-one courses of radiation therapy (75.6%) produced objective response, and 10 courses (24.401,) failed to affect the tumors. Regression was observed with doses as low as 1,500 r in 1 week. Most of the failures, how- ever, occurred when a less than 2,000-r tumor dose was delivered. There were no failures to respond with a tumor dose greater than 2,000 r (Table 3).

TABLE 3 TUMOR RESPONSE IN RELATION TO

RADIATION DOSE USED IN TREATING PATIENTS WITH RHARDOMYOSARCOMA

Total No resp., Resp., Dose, no. no. no. r courses courses" courses*

Embryonal type

1.001-1.500 4 3 1 500- 1,000 3 3 0

- I - - - -,- 1,5 01 -2,000 12 4 8 2,001-2,500 7 0 7 2,501-3,000 5 0 5 3,001-3,500 4 0 4 3.501-4.000 4 0 4 4;001-4;500 4,501-5,000

TOTAL Adult type 1,100-1,500 1,501-2,000 2,001-2,500 2,501-3,000 3,001-3,500 3,501-4,000 4,001-4,500 4,501-5,000 5,001-5,500 5,501 -6,000 6,001-6,500

TOTAL

1 1

41

5

-

2 0 2 2 2 1 2 1 0 1 -

18

0 1 1 0 - -

10 (24.4) 31 (75.6)

5 0 2 0

0 1 0 2 0 1 0 0

1 0

8 10 - -

*The figures in parentheses are percentages.

TUMOR RESPONSE IN RELATION TO RADIATION DOSE USED IN TREATING PATIENTS WITH SYNOVIAL SARCOMA.

FIBROSARCOMA, AND SPINDLE CELL SARCOMA

Dose,

~~~~~

Total No resp., Resp., no. no. no.

r courses courses courses

Synovial sarcoma 600-1,000 3 2 1

1,001-1,500 7 1 6 1.501-2.000 4 2 2 2:001-2: 500 6 1 5 2;501-3:000 6 3,001 -3,500 1 3.501-4.000 1

2 1 0

4 0 1

4;OO 1-4; 500 2 0 2 - TOTAL 30

Fibrosarcoma 1,200- 1,500 3 1,501-2,500 1 2,501-3,500 6 3,501-4,500 4 >4,500 2

TOTAL 16 Spindle cell sarcoma 1.200-1 .SO0 1

-

i:501-2$00 3 2,001-2,500 2 2.501-3.000 5

- 9

2 1 2 0 0

5

1

-

2 1 3

- 21

1 0 4 4 2

11

0 1

-

1 2

3;OO 1 -3;SOO 3 1 2 3,501-4,000 3 1 2 4,001-4,500 3 1 2 4,501-5,000 2 0 2 > 5,000 1 1

TOTAL 23 10 13 -

0 - -

Of the 41 courses of treatment in which there was objective response, the duration of response could be evaluated in 22. The average duration of response was 3.8 months, with a range of 1 to 27 months. The duration of response did not seem to depend on the dose delivered. No definite evaluation of com- bined chemotherapy and radiation treatment could be made from this study since the num- ber of cases so treated was small.

In the group of patients with adult type rhabdomyosarcoma, the age of the 13 patients varied from 21 to 92 years. Eighteen courses of radiation therapy were given. One treat- ment course was combined with nitrogen mus- tard. The dose range was from 1,100 r in 13 days to 6,100 r in 55 days. Ten courses of radiation therapy produced regression, while 8 courses failed to result in a response. The lowest dose that produced tumor regression was 3,000 r.

In 8 of the 10 treatment courses in which the patients showed objective response, the duration of this response could be evaluated.

I82 CANCER January-February 1962 Vol. 15

T h e average duration of response was 12.3 months, with a range of from 3 to 39 months. When the duration of regression was corre- lated with the dose delivered, no pattern emerged.

Gmu/) 3. Leiomyosarcoma. Five patients re- ceivcd 12 courses of radiation treatment (Ta- ble 1). The dose ranged from 700 r in 5 days to 4,700 r in 34 days. Five courses of treatment 1)roducect no response and 7 resulted in im- 1wolement for an iiveriige of 4 months' clura- lion with a iange ol' 2 to 7 nionths. With this sniall number of treatment courses, i t was dif- ficult to determine the relationship between dose level and response of the tumors.

Grorij) 4 . Synovial Sarcoma. 'Twclve patients receivctl 30 courses o f irradiation with a dose iange of 600 1- in 5 days to 4,300 r in 25 days. In <$ of the courses, the patients failed to re- spond, while 21 courses produced favorable response (Tables 1 and 4). X number of lesions resI)onded to the lower closes but the majority of thc patients who showed Favorable objec- tive respome to therapy received tloscs greater than 2,000 r.

In 19 ol the 21 courses of treatment the du- ration of regression of the tumors could be evaluated. T h e average duration ol regression W;I\ 6.8 months with a range of 1 to 27 months. Ag;iin, the tluration of objective response fol- los~etl no pattern in relation to the dosage schedule.

Group 5. Fibrosarcoma. Seven patients re- ceived 16 courses of treatment with a dose range of 1,200 r in 13 c1,iys to 5,300 r in 45 t la)c . Five treatment courses did not produce ;in objective response (Tables 1 and 1). T h e majority of the patients who responded fa- vorably received a tumor dose greater than 1,500 r in 2% weeks. No lesion €ailed to re- spond to in adiation with a (low greater than 3,500 1' i n 23 days.

'I'lie duration of regression was known in 10 of the 11 courses that produced favorable response. The average duration of regression was 3.4 months with a range of 2 to 8 months. In .ill o l the 4 instances in which there was a rcniiwion period longer than 6 months the patients received n tumor dose greater than 3,000 r.

GTOUP 6. Spindle Cell Sarcoma. Fifteen pa- tients received 25 courses of treatment. T h e (low ranged from 1,200 r in 8 days to 5,100 r in 27 days. Regression of tumor was obtained in IS treatment courses while 10 courses of irradiation did not result i n improvement

(Tables 1 and 4). Most of the failures occurred when less than 3,000 r was delivered. T h e duration of regression was known in all but 2 instances. The average duration of regres- sion was 4.7 months with a range 01 2 to 9 months. When the duration of regression was correlated with the dose delivered, i t was found that patients with the longer durations of regression received a tumor dose greater than 3,500 r.

DISCUSSION

Soft tissue sarcomas presented a wide range o f rarliosensitivity, not only among the vni - 011s histological types of neoplasms, but also within each histological category. Liposai c 0111;i

(including myxoliposarcoma) showed the grca t- est degree of radiosensitivity among the sott tissue sarcomas studictl.

In the group of rhabdomyosarcomas, the data indicated that the embryonal type w a s more re5ponsive to radiation than was the adult type, but the remission was usually short-lived chiefly because of the aggressive- ness of the disease, resulting in widespread metastases and patients' early death.

Although the number ol cases in each group does not allow for intensivc statistical c ~ a l u a - tion, and despite the wide variation of sen- sitivity in each histological group, the impres- sion is gained that more favorable responses were obtained when a higher dosage level wits delivered, i.c., more than 2,000 r in approxi- mately 2 weeks in the cases of l ipar r to im, cnibrysn;d type of rhabdornyosarcorna, ant1 synoviosarconia; inore than 2,500 r in approxi- mately 2% wetlks for fibrosarcoma; and mole than 3,000 r in approximately 3 weeks for the adult type of rhabdomyosarcoma and for cpin- clle cell saicoma.

Tn the over-all group of 104 patients, 3 o u t of 4 treatment rourses resulted in objective and symptomatic improvement with an avcr- age duration of 8.4 months. Certainly, radia- tion therapy is worthwhile in the palliative management of soA tissue sarcomas.

Sunm ARY AND CONCLUSIONS

Two hundred twenty-seven courses of radia- tion therapy were administered to 10.1 pa- tients with soh tissue sarcomas, chiefly for palliation of residual, recurrent, or metastatic lesions. There was an over-all response rate of 74% with an average duration of response of

No. 1 RADIATION PALLIATION OF SOFT TISSUE SARCOMAS - Pewy Q Chu 183

8.4 months. T h e best palliative result was obtained in the group with liposarcomas in whom 75 of 87 courses of therapy produced a response rate of 86.2% and an average dura- tion of remission of 11.6 months.

The soft tissue sarcomas showed a wide range of radiosensitivity among the various histological categories and also among the lesions of the same histological type. The liposarcomas showed the greatest degree of radioresponsiveness with regressions appearing in many instances with doses less than 2,000 r. In the over-all group a greater number of favorable responses or a longer remission pe-

riod was obtained when a close higher than 3,000 r was delivered.

REFERENCES

1. BOWUEN, L.: Diagnosis and treatment of soft part sarcomas. Virginia M . Mopltlily 81: 463-470, 1954.

2. CADE, S.: Soft tissue tumours; their natural history and treatment; president's address. Proc. Roy. Soc.

3. LIEBERMAN, Z., and ACKERMAN, L. V.: Principles in management of soft tissue sarcomas; clinical and pathologic review of 1.00 cases. Surgery 35: 35Q-365, 1954.

4. PACK, G. T.: End results in treatment of sarcomata of soft somatic tissues, J . Bone ch Joint Surg. 36-A: 241- 263, 1954.

Med. 44: 19-36, 1951.