Ben M. Peckham

Radiation dosage and complications in cervical cancer therapy

Computerized dosimetry in 346 patients treated by a combination of intracavitary and supervoltage radiotherapy has permitted a detailed analysis of dose delivered. The radiation delivered to the bladder, rectum, paracervical area, and the pelvic wall is described for a technique in which a calculated bladder and rectal tolerance was used as the limiting factor for total central dose. Rectovaginal and vesicovaginal fistulas occurred in only 1.4 per cent of the patients, but other serious bowel and ureteral complications were seen in 6.4 per cent. These later complications occurred significantly more frequently when intracavitary therapy was emphasized, producing high paracervical total doses. No individual correlation between dose delivered and complications could be demonstrated.

The Relationship of Reactions to Complications in the Radiation Therapy of Cancer of the Cervix

A review was made of the reactions and complications associated with high-dose radiation therapy of invasive carcinoma of the cervix in 410 patients. In all patients a combination of intracavitary and external therapy had been given. Either a bowel or urinary tract reaction or both developed in 133 of the 410 patients; one or more complications occurred in 94. As the severity of bowel reactions increased, the subsequent complication rate increased significantly, but 39% of those with bowel complications and 88% of those with urinary tract complications had no warning reaction.

Radiation reactions in cervical cancer therapy

Abstract Between 1961 and 1969, there were 410 patients treated for invasive squamous cell carcinoma of the cervix with either intracavitary therapy alone or in combination with external radiation. This group of patients was reviewed for reactions occurring during treatment as well as one month after completion of treatment. The reactions were subdivided into mild, moderate, and severe. As the gastrointestinal reactions became more severe, the chance for a subsequent complication increased significantly. Though patients had no problems during the course of radiation therapy, it appears a certain per cent will still develop complications later. The same relationship was not observed for the genitourinary system. The majority of patients developing a genitourinary complication had no significant symptoms during the reaction period.

Cellular metabolic activity— A new basis for screening of vaginal cytology?

Abstract The hypothesis that a major difference in metabolic activity exists between cells shed from normal surfaces and these desquamated from epithelial abnormalities such as dysplasia, carcinoma in situ, and frank malignancy has been tested in 93 patients. It has been demonstrated that incorporation of the amino acid C 14 L-leucine is significantly greater in cells obtained from women bearing known epithelial abnormalities in the genital tract, than it is in cells obtained from apparently normal women. The possibility that this difference will permit mass screening of the female population when combined with home cell collection techniques has been discussed.

The kinetics of the generative compartment of the estrogen dependent vaginal epithelium.

The kinetics of the generative compartment of the vaginal epithelium in estrogen treated rats were studied using 3H-thymidine autoradiography. Castrate rats were grouped and treated with varying doses of diethylstilbestrol for a period of two weeks to create a steady state in the vaginal cell population. 3H-thymidine was then made continuously available (hourly injections) and the animals were sacrificed at intervals up to 48 hr. In some renewal systems, the generative compartment contains two populations of cells, one which continuously cycles and another which is in a state of dormancy until a stimulus is applied which activates this population to divide. In an attempt to determine if the basal cell layer of the hormone-dependent vaginal epithelium consists of one population of cells or if it contains two morphologically identical but functionally different cell populations tritiated thymidine was made constantly available for a period of time approximately equivalent to the maximum generative cycle time of the population. If the basal layer is a single cell population consisting exclusively of proliferating cells, continuous exposure to tritiated thymidine for a period of time equivalent to the maximum G2 + M + G1, of the population should result in complete labeling. If, however, it contains a resting reserve population the per cent of labeled cells should reach a plateau at some level less than 100 per cent. It is apparent from the data that complete labeling was attained. It was found in a previous study that labeling index increased with increasing dosage of estrogen. The present study indicates that this increase in labeling index associated with increasing estrogen stimulation was caused by progressive shortening of the generative cycle time rather than by activation of a second population or resting reserve. It seems, therefore, that the hormone-dependent generative compartment of the vaginal epithelium is a homogeneous population of actively proliferating cells.

Isolated vaginal cuff recurrence following therapy of endometrial adenocarcinoma

Abstract A group of 155 patients with Stage I and Stage II adenocarcinoma of the endometrium was treated with preoperative intrauterine, endocervical, and upper vaginal radiation, followed by total abdominal hysterectomy and bilateral salpingoophorectomy. Complications of the therapy were minimal. There were 3 recurrences involving the vagina (1.9 per cent) but none was an isolated vaginal cuff recurrence. On the basis of this experience, as well as that of others, the authors favor preoperative intracavitary radiation, designed to include the vaginal apex, in the therapy of endometrial carcinoma.

Changes in vaginal cellular activity elicited by varying doses of natural and synthetic estrogens.

Abstract Castrate rats were treated with varying doses of 17 β estradiol and diethyl-stilbestrol for a period of two weeks to allow steady state conditions to pertain in the vaginal epithelial cell population. To estimate the cellular proliferation rate, the number of cells in DNA synthesis in the basal layer was estimated for each dosage level using tritiated thymidine autoradiography. A sigmoidal dose response was noted which was almost identical for the two hormones when the percent labeled basal cells was plotted against log dose. When the dose of estradiol exceeded 0.5 μg/day or the dose of diethylstilbestrol exceeded 1.0 μg/day, toxicity was apparent. Vaginal epithelial thickness, measured in the same animals, correlated almost perfectly with this labeling index at each dosage level, suggesting that epithelial thickness is essentially a pure function of the cellular proliferative response to these hormones.

High-dose radiotherapy for carcinoma of the cervix. Method and results.

A method of radiotherapy of invasive carcinoma of the cervix has been devised utilizing rectal and bladder tolerance as the limiting factor for total central dose. The resulting milligram hours and paracervical doses have been high, especially when intracavitary therapy has been emphasized. The survival statistics on 450 patients treated between 1961 and 1967, mostly by this plan, are good but show that no striking improvement has resulted from the increased doses.

Evaluation of intra-amniotic administration of 120 gm of urea with 5 mg of prostaglandin F2α for midtrimester termination of pregnancy between 20 and 24 weeks' gestation

The occasional finding of signs of life in fetuses delivered following intra-amniotic administration of 80 gm of urea and 5 mg of prostaglandin F2 alpha suggested that the dose of 80 gm of urea was inadequate beyond the nineteenth week. Protocol modifications were made, and the metabolic effects of intra-amniotic administration of 120 gm of urea used beyond the nineteenth week were compared to those of the 80 gm dose of urea used in patients prior to the twentieth week. The 120 gm urea dose was well tolerated. The peak blood urea nitrogen (at 4 hours after instillation) was higher with 120 gm of urea (36.4 mg/dl) than with 80 gm of urea (24.6 mg/dl) (p less than 0.05). Small decreases in the platelet count (14% of control) and serum fibrinogen (11%), sodium (2%), potassium (7%), and carbon dioxide (11%) levels and a 5% increase in peak serum osmolality were found. Following the change in protocol, fetal heart activity has been absent at 3 hours after instillation in all cases less than 24 weeks from the last menstrual period.

The heterologous transfer of cervical carcinoma with certain histologic observations.

I N THE fall of 1956 we elected to change our therapy of cervical carcinoma from the standard program of external x-irradiation followed by internal application of radon to a modification of t,he plan developed at Washington Univeisity.lp 2 The latter includes parametrial injection of radioactive colloidal gold, local application of radiocobalt, and, for selected Stage I and early Stage II lesions, radical hysterectomy with pelvic node dissection. The work reported here arose from an attempt to determine whether radical hysterectomy and lymph node dissection following parametrial radiation are valuable parts of this regime, Among the questions to be answered in this regard were these: