Five hundred twenty-six patients with invasive cervical cancer, treated at the University of Kentucky from 1964 to 1976, were followed 2-12 years after therapy. One hundred and sixty patients (3 1 %) developed tumor recurrence. Recurrent cancer was noted within 1 year after therapy in 58% of patients and within 2 years of treatment in 76% of patients. Only 6% of patients with recurrent cervical cancer survived 3 or more years. Stage of disease, cell type, lesion size, and the presence of lymph vascular space invasion by tumor cells were all shown to be prognostically significant. The addition of extrafascial hysterectomy to radiation therapy significantly decreased the incidence of recurrence in stage IB cervical tumors 5 cm or more in diameter. Analysis of this data suggests that radical hysterectomy and pelvic lymphadenectomy is as effective as irradiation only in the treatment of large cell squamous carcinomas 2 cm or less in diameter.Cancer 44:2 354 -236 1, 1979.

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron‐emitting radioactive isotope, californium‐252 (Cf‐252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel‐shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5‐year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf‐252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron‐enhancing chemicals.

Five hundred twenty-six patients with invasive cervical cancer, treated at the University of Kentucky from 1964 to 1976, were followed 2-12 years after therapy. One hundred and sixty patients (3 1 %) developed tumor recurrence. Recurrent cancer was noted within 1 year after therapy in 58% of patients and within 2 years of treatment in 76% of patients. Only 6% of patients with recurrent cervical cancer survived 3 or more years. Stage of disease, cell type, lesion size, and the presence of lymph vascular space invasion by tumor cells were all shown to be prognostically significant. The addition of extrafascial hysterectomy to radiation therapy significantly decreased the incidence of recurrence in stage IB cervical tumors 5 cm or more in diameter. Analysis of this data suggests that radical hysterectomy and pelvic lymphadenectomy is as effective as irradiation only in the treatment of large cell squamous carcinomas 2 cm or less in diameter.Cancer 44:2 354 -236 1, 1979.

Seventy-five patients with bulky barrel-shaped Stage IB cervical cancers, treated at the University of Kentucky from 1965 to 1981, were the subjects of this investigation. Thirty-two of these patients were treated with radiation therapy alone and 43 were treated with radiation followed by extra-fascial hysterectomy. There were no significant differences in age, gravidity, or tumor cell type between the two treatment groups. Patients were seen at regular intervals from 2 to 11 years after treatment and none were lost to follow-up. Recurrent cancer was noted in 47% of patients treated by radiation alone as compared to 16% of those treated with combined therapy (P less than 0.01). The incidence of pelvic recurrence was reduced from 19% to 2% and extrapelvic recurrence from 16% to 7% in patients treated by combination therapy. No rectal or urinary tract fistulae were noted after extra-fascial hysterectomy. The findings of this study suggest that the use of extra-fascial hysterectomy following radiation therapy in patients with bulky Stage IB cervical cancer causes a significant reduction in tumor recurrence without producing an increase in treatment-related complications.

Radiation-induced tumor regression was evaluated as a prognostic factor in 200 patients with invasive cervical cancer treated at the University of Kentucky Center during the years 1973-1977. Radiation responses were classified as complete (Type A), intermediate (Type B), or incomplete (Type C) based upon pelvic examination findings one month following completion of therapy. Patients with Type A response to radiation had a recurrence rate of 5%, as compared with 27% in patients with a Type B response and 85% in patients with a Type C response. The direct relationship between radiation response and the incidence of tumor recurrence was observed in all stages of disease. Seventy-five percent of patients with Stages IB and IIB disease and a Type C response to radiation developed recurrent cancer, and tumor recurrences were confined to the central pelvis in the majority of cases. Patients with keratinizing squamous cell cancers had the lowest incidence of complete response to radiation. These findings suggest that careful observation of cervical cancer throughout radiation therapy can provide prognostically significant information concerning radiation-induced tumor regression. The therapeutic implications of this data is discussed.