February 17, 2023

Evolution of Radiation Treatments for Uterine Cancer

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Ismail Kazem, MD, FACR


Over the past century, surgery and radiation therapy have been the mainstay of treatment for cancer of the uterus. Only recently has adjuvant platinum-based chemotherapy been included in the treatment.

By a strike of historical fate, the relationship between surgery and radiation therapy was born around the turn of the 20th century and has evolved ever since. This history note describes how both surgery and radiation treatments enhanced the value of each other and complemented their roles.

In 1895, W.C. Roentgen discovered X-rays. In 1896, Henri Becquerel reported natural radioactivity in uranium compounds which led Marie and Pierre Curie to isolate radium from pitchblende. As Becquerel carried a sample of pitchblende in his vest pocket, he noticed that an erythema had developed on the adjacent skin. The biological effects of X-rays and radium radiation were unraveled. As early as 1901, The Macmillan Company of New York published a book titled, “The Roentgen Rays in Medicine and Surgery as an Aid in Diagnosis and as a Therapeutic Agent” by Francis H. Williams, MD.

Surgery versus radiation therapy:

In 1903, Margret Cleaves of New York1 used radium to treat patients with uterine cervix carcinoma. E. Wertheim of Vienna2 developed the radical total hysterectomy in 1898. The high operative mortality associated with major surgery prior to antibiotics and modern anesthesia limited the application of radical surgery to a small number of gynecologists in selected cases3. This presented the opportunity to develop radium techniques and prove the efficacy of radiation therapy in the treatment of uterine cancer.

The limitations of intracavitary radium were quickly recognized, thanks to surgical pathology information from hysterectomy specimens. As early as 1924 supplementary X-ray treatment to the lateral pelvic wall was introduced for the first time at the Radiumhemmet clinic in Stockholm.

During the years that followed the second world war, both surgical and radiotherapeutic techniques were revolutionized. On the surgical front, the risk of primary surgical mortality was minimized thanks to better selection, better understanding of surgical physiology, better anesthesia and available antibiotics. This revived the interest in surgery as an alternative to radiotherapy in early stages of cancer and introduced pelvic exenteration procedures for the advanced, yet salvageable stage (Meigs 19544, Brunschwig 19565).

On the radiotherapeutic front — physical, radiobiologic and technical refinement paired with computer technology achieved a degree of sophistication and precision for the delivery of safe and effective treatment with minimum of side effects. Among these new technologies for external beam radiation are image-based treatment planning, 3D conformal radiation therapy, intensity-modulated radiation treatment (IMRT), as well as image-guided and adaptive radiation treatments. Proton beam and particle therapy are also available in some centers.

Intracavitary treatments have also become safer, accurate and patient friendly. By replacing radium with other radioactive isotopes (e.g., iridium-192) and applying programmable, after-loading, high-dose rate sources, it is possible to deliver treatment on an outpatient basis.

The fruitful teamwork relationship developed over the past century between the gynecologist and the radiation oncologist has resulted in optimizing the management of uterine cancer. This is reflected in the guidelines of both the International Federation of Obstetrics and Gynecology and National Comprehensive Cancer Network.

References

  1. Cleaves, Margaret. “Radium: With a Preliminary Note on Radium Rays in the Treatment of Cancer,”  Medical Record 64, 1903; 601–606.
  2. Wertheim, E. “A Discussion on the Diagnosis and Treatment of Cancer of the Uterus,” British Medical Journal, July 1905.
  3. Kazem, I. “From Incurable to Preventable, the Success Story of Cancer of the Uterine Cervix," Journal of Gynecology and Obstetrics, July 2022;10(4):183–185.
  4. Meigs, J.V. “Carcinoma of the Cervix,” New England Journal of Medicine, 1944;230:577–582, 607–613.
  5. Brunschwig, A. “Complete Excision of Pelvic Viscera for Advanced Carcinoma,” Cancer, 1948;1:177–183.