GYNECOLOGIC ONCOLOGY 2,324-330 (1974)

Afterloading and Radium Substitutes1

NORMAN SIMON, M.D.

The Mount Sinai School of Medicine, New York, New York 10029

Received March l&l974

The Heyman packing technique is the most useful intracavitary method of ir- radiating endometrial cancer. The main disadvantage of the classical Heyman tech- nique is the unnecessary exposure of personnel to radiation. Substitution of radium by cesium-137 permits afterloading. The endometrial cavity can be packed with hollow tubes with bulbous ends dimensionally similar to Heyman applicators, but able to be afterloaded with miniaturized sources of cesium-137. Afterloading re- duces exposure of personnel to radiation, allows more accurate placement of radio- active material, and permits better teaching of the procedure.

Radium is becoming obsolete, and new directions for research on endome- trial cancer must include the reevaluation of intracavitary radiation for this tumor. Intracavitary radiotherapy of the uterus is well defined for cancer of the cervix, but this form of treatment is in a muddle for cancers of the endome- trium.

The flattened pear-shaped radiation dose distribution resulting from an in- trauterine tube and vaginal sources seems to irradiate satisfactorily the cer- vical cancer and its extension to the parametria. But this flattened pear-shaped distribution is not ideal for the irradiation of an irregular endometrial cavity involved by adenocarcinoma.

The ovoid dose distribution around a tandem or intrauterine tube would ir- radiate satisfactorily a superficial tumor of the lining of a normal uterine cav- ity, but when this cavity is enlarged or irregular other arrays of radioactive sources are preferable. Among these arrays are multiple linear tubes, flexible tubes which can be converted into triangles of J-shape in the cavity, springed devices which spread to conform roughly to the shape of the cavity, expan- dable balloons to be inserted and filled with liquid radionuclides, and other expressions of man’s imagination and experience in filling this cavity.

The intracavitary method of most acceptance and usefulness has been the packing technique of the Radiumhemmet of Stockholm, the technique of Heyman. For half a century many institutions throughout the world have been packing the uterine cavity with Heyman capsules containing radium. The definitive description of the Heyman technique is contained in an article by Heyman, Reuterwall, and Benner published in 1941 in Acta Radiologica. Here the experience and technique are detailed making this article a vade mecum for the radiotherapists and gynecologists who use the Heyman

1 This work was supported by the Hoffman Radiation Research Fund and by the Jack Martin Fund.

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Copyright @ 1974 by Academic Press, Inc. All rights of reproduction in any form reserved.

AFTERLOADING AND RADIUM SUBSTITUTES 325

method. It was my privilege to learn how to pack the uterine cavity under the gracious guidance of James T. Heyman, himself, in 1949 at the Radium- hemmet, and even then we recognized problems with the technique. The Heyman applicator is a steel capsule containing radium, and a thin wire leads from this capsule through the cervix and out the introitus. The capsules are in- serted with a rigid and clumsy holder, and they are packed tightly to distend the uterine cavity with as many capsules as the cavity will tolerate. Each cap- sule is radioactively hot containing 5-10 mg of radium. The packing proce- dure results in a dose to the radiotherapist of 25-100 mrads for each procedure as measured by a pocket dosimeter. Even if cesium-137 is substituted for radium in the classical Heyman capsule, as currently used in the Radium- hemmet, there is little advantage as far as exposure to personnel is concerned if afterloading is not used.

The disadvantages of packing in the classical Heyman manner are obvious. First of all, the radiation exposure to operating room personnel, and to others, is unnecessary and undesirable. In the wise recent words of Ralston Paterson, the use of live radium in the treatment of cancer of the uterus is the last bas- tion of unnecessary radiation to the radiotherapist and his associates.

Another disadvantage of the classical Heyman technique is its inaccuracy. The prudent radiotherapist must work fast to minimize exposure, and such haste decreases the accuracy desired in most surgical procedures.

It is not only the radiotherapist who is inordinately and unnecessarily ex- posed to radiation, but also the other operating room personnel, including nurses and anesthesiologists; transporters, diagnostic X-ray personnel, recov- ery room attendants, nurses, and other personnel in the hospital are also unin- tentionally, unnecessarily, and sometimes unknowingly exposed.

In the procedure of after-loading, hollow tubes and capsules are inserted into the cavity, and subsequently, after establishing the appropriate position of the hollow applicators, the radioactive material is inserted when the patient is in bed in her own room where only she receives the radiation. Afterloading enables the uterine cavity to be irradiated without exposing the personnel in the operating room, in the recovery room, and elsewhere.

What’s wrong with radium for afterloading? Firstly, radium has inherent disadvantages, accepted and expressed by many regulatory agencies and most recently by the International Working Party on the Use of Radionuclides and Afterloading Techniques in the Treatment of Cancer of the Uterus in Devel- oping Areas. This body makes the simple statement that “The continued use of radium-226 is undesirable in the treatment of cancer of the uterus. The disadvantages of radium are now well recognized and the elimination of this material will not only lead to improved radiation protection of the staff but may well encourage the increased use of intracavitary radiotherapy. Health authorities in developing areas are urged to refrain from purchasing radium to make provision for the purchase of suitable substitutes.” Secondly, radium is particularly unsuitable for afterloading multiple capsules of Heyman because of the thickness required of the radium capsule to assure integrity of the source. Very thin tubes are needed for afterloading, and high specific activity

326 NORMAN SIMON

radionuclides must be used as substitutes for the radium. Sufficient minia- turization of radium for afterloading Heyman applicators is impossible.

In our modified Heyman capsules for afterloading, the bulbous plastic cyl- inder of the same size and shape as the original Heyman capsules has a long thin hollow plastic tube leading from the capsule, instead of the braided wire. A thin removable nonradioactive steel wire in the plastic tubing and capsule provides structural rigidity for easy insertion of the capsule into the uterus. The plastic tube and its inactive wire provide a handle for the insertion of the capsule, making this insertion for packing more easily controlled than with the usual Heyman applicator and its bulky inserting device. After the uterine cavity has been packed with these modified Heyman applicators, appropriate control X-ray films are made, and, later, the inert wire is replaced by the dimensionally similar l&gauge steel tubing containing radioactive cesium at its tip. This last part of the procedure is done in the patient’s own room.

In the usual treatment of a patient with postmenopausal bleeding sugges- tive of carcinoma of the endometrium, the diagnosis almost always must be es- tablished by dilatation and curettage under anesthesia. Since frozen section of the curettings is not universally considered diagnostic, the radiotherapist or gynecologist waits a day or two for the final pathology report. Then, if packing of the uterine cavity with radioactive material is indicated, the patient must be anesthetized again to pack the uterine cavity with classical Heyman appli- cators. In contrast, when afterloading applicators of the modified Heyman type are used, they can be inserted at the time of the original dilatation and curettage for they are free of radioactive material. Later they may be loaded with cesium-137 without discomfort to the patient. If the curettings prove to be benign, the blank capsules may be removed without irradiating unnec- essarily.

The radioactive material used must have higher specific activity than radium in order to provide sufficient miniaturization to afterload in multiple capsules. Some gamma emitters which could be useful in high enough spe- cific activity for afterloading include cesium-137, tantalum-182, cobalt-60, and iridium-192. We have elected to concentrate on the development of 13’Cs sources, since this isotope has a suitably long half-life, 30 yr, and a shielding requirement which is less than that of radium. Encapsultation of miniature high specific-activity cesium sources has been a problem until recently, but our sources are comprised of 13’Cs incorporated in porous glass in a cylinder 1.5 cm in length and of such narrow diameter that it fits in the lumen of l&gauge needle tubing. The porous glass absorbs a solution of 13’Cs in tiny chambers and when the glass is annealed the cesium is permanently sealed in the chambers. This source and its encapsulation satisfy the recent rigid cri- teria of the American National Standards Institute, subcommittee N44.2, for integrity of sealed sources of radioactive material, In our devices the activity of the cesium to be loaded into each capsule is equivalent to 10 mg of radium (25 mCi of 13’Cs).

Thus far, in our feasibility studies, we have treated over 70 patients with carcinoma of the uterus, and we have found the procedure practical and analo- gous to the Heyman technique in early clinical response.

AFTERLOADING AND RADIUM SUBSTITUTES 327

In the early prototypes of the capsules difficulty was encountered in making sure the capsules would not separate from the tubes at the time of removal on completion of treatment. More recently, the bulbous capsule has been ul- trasonically welded to the plastic tube, and this bond has been effective.

Irradiation of the vagina is usually considered indicated in the treatment of endometrial cancer because of the established incidence of vaginal metas- tases as one of the routes of spread and recurrence. No single method of vaginal irradiation has been universally accepted. However, in endometrial cancer, two views are held concerning radiation of the vagina; some irradiate only the upper vagina, the fomices. Another view holds that the entire vagina should be irradiated. We have elected to develop a compatible system of ir- radiating the fomices with Manchester-type ovoids, but afterloaded with our miniaturized 13’Cs sources. In this method, we use an inflatable plastic cuff, a polyvinyl chloride plastic doughnut. Attached to the periphery of the doughnut are two vaginal ovoids containing plastic tubes for afterloading. When the uterine cavity has been packed with the modified Heyman appli- cators, the deflated doughnut is inserted into the vagina and adjusted against the surface of the cervix. The ovoids are fixed in the fomices semirigidly when the doughnut is inflated by distension with a radiopaque solution (about 20 cc). This inflatable “colpostat” is compatible with our system for treating cancer of the cervix, as well.

The protruding afterloading tubes are taped on the patient’s thigh, a Foley catheter lies in the bladder. Stereoscopic and orthogonal roentgenograms of the pelvis show the position of the afterloading tubes and ovoids. These films are used for immediate “eyeball” determination of the suitability of the posi- tion of the devices, they are subsequently used for calculation and estimation of dose. Information from these films provides data for computer read-outs of the detailed distribution of radiation around the sources. Only after the posi- tion of the applicator has been verified as satisfactory, and after the patient has been returned to the privacy of her own room, are the dummy wires removed and rapidly replaced by radioactive cesium sources. The loading is done with the radiotherapist protected behind a shielded mobile afterloading cart.

DOSIMETRY

In contrast to the cervix, the dosimetry in endometrial cancer is much more an art than a science.

We still use the data of Heyman from the classical paper of 1941 to deter- mine when the radioactive material is removed, i.e., the exposure dose. In order to keep our data reproducible, we try to give a single dose equivalent to three times the exposure dose described by Heyman in that classical paper. After the intracavitary radiation, most of our patients had a hysterectomy within a few days. This enabled us to verify the positioning of our sources.

In addition, we attempt to make a detailed analysis of the dose distribution by direct in viva measurement with miniaturized thermoluminescent dosim- eters (LiF or CaF). We also make detailed dose read-outs by computer in at least two planes, the data being obtained from the stereo and orthogonal films. The anatomy is identified by inserting a radiopaque seed in an identifiable

328 NORMAN SIMON

portion of the cervix to relate the position of the sources to the OS. Radiopaque material in the Foley bag of the catheter and in the inflatable cuff of the “col- postat,” radiopaque material in the rectum, and dummy wires in the appli- cators all help in the evaluation of the position of the sources in relationship to the anatomy.

Our observations on patients thus far treated have established the safety of exposing the uterus to a dose equivalent to three times the milligram hours specified by Heyman. As an example, a uterine cavity which would hold 10 capsules, each containing the equivalent of 10 mg of radium, would receive an exposure dose of 5000 mg hr in 2 days. Hysterectomy following within a day or two of the removal of the radioactive material has been tolerated by the patient. As yet, we have seen no bowel injuries directly ascribable to this dose.

EXTERNAL RADIATION

I would like once again to quote the words of Dr. Ralston Paterson, the teacher of so many radiotherapists, when he stated that “intracavitary radia- tion is a dominant element in the cure of cancer of the cervix . . . alone may cure over 80% of stage I and significant palliation even in advanced stages.” Despite the time-established value of intracavitary radiation, the day of the big machine is here. There are few radiotherapists, even in training, who are unfamiliar with the methods of treating the entire pelvis to high dose with high-energy external beams, from cobalt to betatron, from 1 MeV to 24 MeV. Yet, the role of intracavitary radiation in cancer of the endometrium may still be much more significant than the external beam, and few radiotherapists are masters of intracavitary techniques. The neglect of intracavitary radiation for endometrial carcinoma is partially attributable to the hesitancy of the prudent radiotherapist to subject his personnel and himself to the unnecessary ex- posure of Heyman capsules of the classical type. Now, afterloading can achieve the same therapeutic aim of the Heyman capsule, and allows the preceptor to teach a trainee without the anxieties of radiation exposure.

Further, it is to be pointed out that the determination of actual comparative results of patients who are treated with intracavitary packing in cancer of the fimdus and those who are operated upon without preoperative intracavitary radiation has never been effectively achieved. Why have we been unable to cull from the experience of the many radiotherapists and gynecologists before us the certain determination of which is better, preoperative intracavitary ir- radiation or not? It has been unfeasible, impractical, and virtually unethical for a comparative study to be made when hazardous radium was used. No well-controlled study has been done, but we have relied upon the good judg- ment and evaluation of master clinicians to bias our views in favor of the type of treatment we have personally adopted. Now, afterloading permits us to design a study which will help us to treat a controlled test group with only one variant, viz., the insertion of radioactive material. It is ethical for this study to be done when no previous studies have determined definitely the role or even advisability of preoperative intracavitary radiation.

AFTERLOADING AND RADIUM SUBSTITUTES 329

There is no difficulty in describing elaborately the distribution of radiation around sources as seen in X-ray films, but the interpretation of these findings is another matter. Where do we measure the desired dose? Are we more exact when we specify the absorbed dose at an artificial “point” 1.5 cm from the sources or when we use milligram hours of radium equivalent? Is the rectal dose determinable and is it significant? What is a satisfactory dose rate? Is more than one packing preferable? What is the ideal diameter of the capsules, large or small? These and other questions lead us into fruitful directions for research in dosimetry of intracavitary treatment of cancer of the endometrium.

In summary, afterloading modified Heyman applicators with miniaturized sources of cesium-137 are now practical for packing the uterine cavity in en- dometrial cancer. Radiation safety is increased, exposure to personnel is reduced. Accuracy of placment of packing is improved. Operations and anes- thesias are spared. The procedure of packing the uterine cavity is simplified, and now it can be taught without unnecessary exposure to trainees. Con- trolled studies are made feasible with afterloading. Radium is obsolete in the classical Heyman technique, and indeed for the treatment of endometrial cancer.

REFERENCES

1. SIMON, N., BRUCER, M., AND HAYES, R., Radiation and leukemia in carcinoma of the cervix, Radiology 74,6, 905-911 (1960).

2. BOTSTEIN,C.,SCHULTZ,R. J.,AND SIMON,N., Theuseofadiamond shapedfieldin hdia- tion of pelvic organs, particularly in carcinoma of the cervix uteri, Amer. J. Roentgenol. Radium Ther. Nucl. Med. 44-47, 87, 1 Jan. 1962.

3. SIMON, N., Exposure of patient and physician by diagnostic and therapeutic devices, Bull. N. Y. Acad. Med. 38,750-752 (1962).

4. SIMON, N., Health aspects of lonizing radiation, Diseases of the neruous system, Monogr. Suppl., 24, (1963).

5. SIMON, N., GRACE, W. J., WARREN, S., DUNHAM,~. L., BRUCER, M., AND QUASTLER, H., Radiation effects-A symposium, N.Y. State./. Med. 64,853-863 (1964).

6. SIMON, N., BLATZ, H., ROACH, J., HARLEY, J. H., SEAMAN,~. B., BRUCER, M., DUNHAM, C. L., WARREN, S., AND QUASTLER, H., Saft procedures in radiation-A panel discus- sion, N.Y. State, J. Med. 64,963-975 (1964).

7. SIMON, N., AND HARLEY, J., Jewelry gold contaminated with radon deposit, J. Amer. Med. Ass. 200, 254-255 (1967).

8. SIMON, N., Afterloading multiple irradiators for the treatment of cancer of the corpus of the uterus: A preliminary report of a new device, J. M. Sinai Hosp. New York, 36, 443-445 (1969).

9. SIMON,N., SILVERSTONE, S. M.,AND ROACH, L. C., Afterloading Heyman applicators, Acta Radial. 10,231-238 (1971).

10. SIMON, N., Afterloading intracavitary radiotherapy of endometrial carcinoma. Panminerua Med. 13,372-373 (1971).

11. SIMON, N., Health maintenance organization-now: A simplified plan for the treatment of cancer of the uterine cervix, In preparation.

12. SIMON, N. [Ed.] Proceedings of a conference on afterloading, May 1971. U.S. Govt. Printing Office, DHEW Publication No. (FDA) 72-8024 BRH/DMRE 72-4, (1971).

13. SIMON,N.,SILVERSTONE,S.M.,ANDROACH,L. &An overviewofafterloadingin radiother- apy, Amer. J. Roentgenol. Radium Ther. Nucl. Med. 114,649-651 (1972).

14. SIMON, N., AND HARLEY, J., Skin reactions from gold jewelry contaminated with radon deposit (1967), in History ofmedicine, by Lester S. King, Penguin Books, Harmondsworth, England, pp. 301-303 (1971).

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15. SJMON, N., AND SILVERSTONE, S. M., An inflatable system for intracavitary treatment of cancer of the uterine cervix, j. Mt. Sinai Hosp. New York, 39,544~547 (1972).

16. SIMON, N., AND SILVERSTONE, S. M., Intracavitary radiotherapy of endometrial cancer by af- terloading Gynecol. Oncol. 1, 13-16 (1972).

17. SIMON, N., AND SILVERSTONE, S. M., Radiation treatment of carcinoma of the uterine cervix, Bull. N.Y. Acad. Med. 49,765, (1973).

18. SIMON, N., Endometrial cancer: A problem in diagnosis, Geriat. Focus, 12, 1, (1973). 19. SIMON, N. [Ed.] Cancer of the uterus in deoeloping areas, Brazil ‘73, Report of the Working

Party and Proceedings of a Conference. Printing Office of the National Cancer Institute, Rio de Janeiro, Brazil, May 1973.

26. BORTOLOT, V. J., SIMON, N., AND SILVERSTONE, S. M., Thermoluminescence dosimetry in medicine and archaeology, Bull. N.Y. Acad. Med., In press.

21. SIMON, N. [Ed.], Cancer of the uterus. In Preparation to be published by the Bureau of Radiological Health, U.S. Dept. of HEW, Scheduled for June 1974 (HEW Contract No. FDA 73-46).

22. SIMON, N., Conference recommends ban on radium, Geriat. Focus 12,l (1973). 23. SIMON, N., SILVERSTONE, S. M., AND BYRNE, R., El Futuro de1 Radio, for presentation at the

Inaugural Meeting of the National Plan for the Elimination of Radium, Caracas, Venezuela, November 16, 1973.