PREOPERATIVE IRRADIATION OF OSTEOGENIC SARCOMA WITH INTRA-ARTERIALLY INJECTED

Case Report NORMAN SIMON, MD, ROBERT SIFFERT, MD, MURRAY G. BARON, MD,

HAROLD A. MII-TY, MD, AND AMIEL RUDAVSKY, MD

YTTRIUM-90 MICROSPHERES

Plastic microspheres containing yttrium90 were injected intra-arterially into an osteogenic sarcoma of the femur to administer preoperative irradiation. Brems- strahlung scans showed radioactivity localized in tumor and lungs. Specimens from the sarcoma and adjacent normal tissue were assayed for radioactivity and dose administered, about 2800 rads to the tumor and 100 rads to the adjacent skin. This method of preoperative irradiation merits further investi- gation.

HE PROGNOSIS IN PATIENTS WITH OSTEO- T genic sarcoma is grave and it may be that no form of therapy aside from prompt amputation is of help. Despite isolated re- ports to the contrary,l radiotherapy, preoper- atively and postoperatively administered, has not yielded predictably better results than surgery alone. Even radical amputation of in- volved extremities i s unavailing in the vast majority of patients because of the develop- ment of pulmonary metastases.

A recent case has afforded us the opportu- nity to study the feasibility of preoperative irradiation of osteogenic sarcoma with intra- arterially injected microspheres of yttrium- goy.

CASE REPORT

A 16-year-old boy had pain and swelling above the left knee for three weeks and a rengenographic examination of the left leg showed a destructive lesion with evidence of new bone formation on the medial aspect of the distal femur. An associated Codman’s sign and a soft tissue mass about 7 cm in its axial diameter confirmed the roentgen diag- nosis of ostenogenic sarcoma. No evidence of

From the Departments of Radiotherapy, Ortho- paedics and Radiology and The Andre Meyer Depart- ment of Physics, The Mount Sinai Hospital, New York, N.Y.

The authors thank Sergei Feitelherg, MD, of the Andre Meyer Department of Physics, The Mount Sinai Hospital, for the dose determinations.

Received for publication May 20, 1967.

metastasis was present. The inguinal nodes were not palpable; the liver was not enlarged and the chest roentgenogram was clear. The peripheral blood count and serum alkaline phosphatase were normal and the erythrocyte sedimentation rate was not rapid.

On December 14, 1966 a percutaneous left femoral arteriogram was performed. The ar- terial puncture was made with the needle di- rected toward the foot so that a catheter could be introduced by the Seldinger tech- nique and advanced into the superficial fem- oral artery. Injection of contrast material showed a bizarre and irregular pattern of ves- sels ending in “tumor lakes”6 within the os- teogenic sarcoma (Fig. 1). The blood supply of the tumor seemed to be derived entirely from the superficial femoral artery. Serial films showed early filling of the femoral vein indicating the presence of arteriovenous shunts within the tumor (Fig. 2). Plastic microspheres 15y in diameter and containing 7 mc of QOY were injected into the left super- ficial femoral artery.

On the day following the intra-arterial in- jection of the beta-emitting SOY Bremsstrah- lung scans425 were made to determine the distribution of the radioactive material in tu- mor and other structures. The entire left lower extremity to the tip of the toes, the trunk and the chest were scanned. Radioac- tivity was primarily localized in the tumor (Fig. 3) although a considerable amount of activity was distributed diffusely throughout both lungs.

453

454 Cancer March 1968 VOl. 21

FIG. 1. Selective superficial femoral arteriogram in which the film is exposed at the end of injection of contrast material. Multiple, irregular and tortuous vessels within the tumor are filled from branches of the superficial femoral artery.

FIG. 2. A film exposed 2 sec later shows early filling of the fcmoral veins (arrows) draining the tumor, indicating arteriovenous shunts within the tumor.

FIG. 3. Scan of leg at site of tumor 24 hours after injection of 7 mc of microspheres into superficial femoral artcry. The radioactivity is concentrated in the tumor.

On December 16, 1966, two days after the arteriogram and injection of 9QY, the tumor was biopsied. During this open procedure specimens of skin, fat and tumor were ob- tained for assay of radioactivity. Also, histo- logic examination of the tumor established it as the expected osteogenic sarcoma.

On December 21, 1966, one week follow- ing the injection of QoY, amputation was ef- fected by disarticulation at the left hip, a level far above any discernible radioactive material.

The amputated extremity was stored for one week after its disarticulation to allow fur- ther decay of the radioactive yttrium before complete study of the specimen by the path- ologists.

For dose determinations samples of tissue,

* Dose determinations for QOY in tissue were derived from the formula D, = 73.8 x C.x E, x T, where D, = dose in rads: C = concentration of isotope in mi- aocuries per gram: E, = average beta energy (0.93 MeV) and T = half-life (2.7 days). This formula as- sumes even distribution of the isotope.

skin, fat and tumor were excised during the biopsy procedure and placed in separate pre- viously weighed plastic test tubes. Each sam- ple weighed a few grams. T h e amount of ac- tivity in each test tube containing its sample was measured in a well counter, counting Bremsstrahlung. The well counter was cali- brated with a known sample of 9OY in suspen- sion.* Activity was corrected for weight and decay to the time of injection. The calculated data are given in millicurie per gram at the time of administration.

T h e dose in the lungs was determined by a comparison of the Bremsstrahlung counts ob- tained over the lungs with those obtained over the tumor in the leg. The detecting crystal of the scanner is collimated and “sees” the same area and volume over tumor or over lung. Even though the lung is less dense than the tumor, its greater thickness permits the reasonable estimation that the weight of tis- sue “seen” by the crystal over tumor and lung in this instance is roughly the same. Now the counts in the lung can be compared directly

No. 3 IRRADIATION OF OSTEOGENIC SARCOMA WITH ""Y Simon et al. 455 to the counts over the tumor. The dose to the tumor is known from the biopsy procedure described above. The activity in the lungs in terms of millicuries per gram can be calcu- lated from the ratios of the external counts over the lung and tumor and from the more direct determination of the activity in the tumor from the biopsy specimen.

A better way to determine the homogene- ity (or inhomogeneity) of the radioactive material within the tumor tissue would have been by autoradiography of sections of the tumor. Unfortunately the complete specimen was not available for this determination, and the biopsy specimen was too small to be a significant sample; however, the scan (Fig. 3) gives some measure of this aspect by inspec- tion but not enough data for exact estimation of dose distribution. We have used an as- sumption of uniform dose distribution throughout the volume of tissue in our dose estimations and calculations. The calculated results are in Table 1 but in the center of the tumor, where the scan shows high activity, the dose is higher than average and in the periphery the dose is correspondingly lower than average. The data from the excised bi- opsy specimens and the scans of the extremity and the lungs indicate the approximate doses in various tissues.

DISCUSSION

Intra-arterial irradiation of tumors has been reported by many investigators. Blanc- hard2 recently detailed the treatment of 31 patients with advanced cancer using QOY mi- crospheres. One of these patients had meta- static carcinoma of the lower end of the femur secondary to a previously operated squamous cell carcinoma of the lung. This patient survived more than two years with- out surgery. In Italy Dogliottis and his associates have treated sarcoma of the lower

TABLE 1. Doses in Tissue

Site Rads

Tumor Lungs Fat near tumor Skin near tumor

2800 5 60

70 100

extremity with intra-arterially injected mi- crospheres of resin containing S2P. A patient with lymphangiosarcoma of a chronically edematous arm has survived 5 years after intra-arterial injection of radioactive yttrium by Herrmann and Ariel.3

The technical procedure of arteriography has become such a useful tool in the evalua- tion of tumors that it provides a convenient preliminary to the direct intra-arterial ir- radiation of these tumors. Apart from its diagnostic value, the selective arteriogram also provides information regarding the blood supply of the tumor, the extent of the tumor and the size of the arteriovenous shunts within the tumor. The latter is of use in predicting the potential leakage of the mi- crospheres into the circulation and may be of help in selecting the size of microspheres to be used. In the case we have described there has been a leakage of approximately 20% of the microspheres through the arteriovenous shunts of the tumor into the lungs. No stud- ies have been made in man on the toler- ance of the lungs to irradiation with microspheres but the lungs should tolerate doses as high as 2000 rads. Such irradiation of the lungs may even be of benefit in the pre- vention of metastasis to the lungs.

Further, the dose distribution is not as homogeneous as from an external beam but is more like the uneven distribution from an implant. Preoperative radiotherapy admin- istered intra-arterially with the short-lived QOY is more rapid than the usually admin- istered external radiation.

REFERENCES

1. Baclesse, F.: Radiation treatment of primary osseous tumors. Radiol . Clin. 28:276-290, 1959.

2. Blanchard, E. L., LaFave, J. W., Kim, Y. S., Frye, C. S., Ritchie, W. P., and Perry, J. F. Jr.: Treatment of patients with advanced cancer utilizing SOY mi- crospheres. Cancer 18:375-380, 1965.

3. Herrmann, J. B., and Ariel, I. M.: Therapy of lymphangiosarcoma of the chronically edematous limb. Am. J . Roentgen. 99:393-399, 1967.

4. Simon, N., and Feitelberg, S.: Scanning Brems- strahlung of intra-arterially injected yttrium-90 mi- crospheres. Radiology 88:719-724, 1967.

5. - , Feitelberg, S., Warner, R. R. P., Green- span, E. M., Edelman, S., and Baron, M. G.: External scanning of internal beta-emitters. J . M t . Sinai Hosp.

6. Strickland, B.: Value of arteriography in diagnosis 33~365-370, 1966.

of bone tumors. Brit . J . Radiol . 32705-713, 1959.