[en] A summary of current evidence indicates that a causal role of intrauterine exposure to radiation in development of malignancy in childhood has not been definitely established. Factors such as individual susceptibility may be important; however, the possibility for the development of leukemia among exposed children adds to the importance of avoiding unnecessary x-ray examinations during pregnancy. Although further evidence is needed, there is the possibility of a link between viral infection and the subsequent development of leukemia in exposed offspring. It appears established that the recent increase observed in the development of clear-cell adenocarcinoma of the genital tract in young females is associated with prenatal exposure to diethylstilbestrol and similar compounds. It cannot be determined at present if these cancers will continue to develop in the vagina and cervix with greater frequency as the exposed population ages, or if cancers at other sites may develop. It has yet to be determined if exposure to steroidal estrogens during pregnancy might play any role in the development of these malignancies. Furthermore, the problem of development of malignancy in stilbestrol-exposed males remains unknown, but at present no association has been established. The exact mechanism that has permitted the development of these rare cancers in stilbestrol-exposed females has yet to be elucidated

[en] We are investigating the potential use of short-lived alpha-emitting radionuclides for the treatment of ovarian carcinoma. These radionuclides transfer dense high ionizing linear energy (high LET) over a short path length without dependence upon cellular oxygen. The alpha-emitting radionuclides chosen were lead-212 and bismuth-212 which are readily available. The radiosensitivities of two ovarian carcinoma cell lines (OVC-1 and OVC-2) was greater with ²¹²Pb and ²¹²Bi than with X-ray therapy. D0, inversely related to the radiosensitivity, was 155 and 240 rads for OVC-1 and OVC-2, respectively. With ²¹²Pb or ²¹²Bi, the slope of the survival curves was steeper. The D0 was 75 and 70 rads after ²¹²Pb and 85 and 95 rads after 212Bi treatment for OVC-1 and OVC-2, respectively. The relative biological effectiveness with alpha irradiation was two to four times greater than with X rays. Unlike low-LET irradiation (i.e., X rays and gamma emitters) the cells had no ability to accumulate or repair sublethal damage. From these experiments it is concluded that a greater therapeutic advantage may be gained with alpha-emitting radionuclides than X rays. Further development of these nuclides may provide for a new form of therapy

[en] Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated

[en] alpha-Emitting radionuclides may be an effective alternative treatment against ovarian carcinoma because they have short half-lives and are densely ionizing, with high linear energy transfer to a depth of several cell diameters without requiring cellular oxygenation. One radionuclide that has been generated and tested in our laboratory in vitro and in vivo is lead 212 (²¹²Pb). Intraperitoneal instillation of ²¹²Pb prolonged survival and totally eradicated tumor in 24% of mice inoculated with the extremely virulent Ehrlich ascites-producing tumor. In vitro ²¹²Pb was two to four times more effective in killing human ovarian cancer cells than x-rays. Irradiation with ²¹²Pb increased the radiosensitivity and chromosomal aberrations of cells. In dogs, intraperitoneal instillation of 2.6 mCi of ferrous hydroxide tagged with ²¹²Pb caused no significant toxicity. It appears that alpha-emitting radionucides such as ²¹²Pb have the potential to be a new and potent treatment of ovarian carcinoma and could be effective in cases that are resistant to conventional chemotherapy or x-ray therapy

[en] A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while in 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions