J. Taylor Wharton

Pelvic exenteration: Analysis of 296 patients

An analysis of 296 patients who had pelvic exenteration discloses a high risk of postoperative complications and death; however, the safety has been improved by technical modifications for urinary diversion and treatment of the denuded pelvic cavity. Recurrent cancer of the cervix or vagina was the main reason for the operation. Prognostic factors were sought to improve selection of patients who are able to withstand operation, tolerate postoperative complications, and remain free of cancer. The five-year survival rate for 296 patients with various types of cancer calculated by the Berkson-Gage method was 56.5 per cent after death from all causes were deducted, the rate was 42.1 per cent. The five-year survival rate for 196 patients with recurrent carcinoma of the cervix calculated by the Berkson-Gage method was 48.3 per cent; after deaths from all causes were deducted, the rate was 33.8 per cent.

Malignant mixed Müllerian tumors of the uterus.

One hundred and eight patients with a diagnosis of malignant mixed müllerian tumors of the uterus treated at the M.D. Anderson Hospital from 1948 through 1977 were analyzed. Pathology was reviewed and subdivided according to the sarcomatous element. No difference in pattern of recurrence or survival could be demonstrated between homologous, heterologous, or undifferentiated sarcomatous elements. Nine patients were treated with only palliative intent due to advanced local disease combined with poor medical condition. Of the remaining 99 patients, 87% had minimum surgical procedures of total abdominal hysterectomy. All but two of these patients had adjunctive radiation either preoperatively or postoperatively. The 5‐year survival rate was 38%. There was frequent upstaging at surgery in all stages except IA. Patients with tumor confined to the uterus at the time of surgery had a 5‐year disease‐free survival of 52%. When there was extension outside of the uterus, the 5‐year disease‐free survival dropped to 28%. The locoregional recurrence rate was 17%.

Carcinoma of the cervix: the effect of age on survival.

Abstract A significant decrease in 5-year survival was found in 265 patients with invasive cervical cancer under the age of 35 compared to 820 over the age of 35 in all stages except Stage I-A and Stage IV. The exact reasons for the differences remain obscure. The greatest number of failures occurred in Stage II-B patients where, despite central control of disease, distant metastases developed. This suggests that the pretreatment evaluation of younger patients, especially those with Stage II-B cancer, should be more aggressive at attempts to detect cancer beyond the usual treatment fields. The poorer prognosis for patients under age 35 could not be explained on the basis of cell type. It was found that patients with large-cell, keratinizing cancers had a somewhat improved survival over patients with large-cell, non-keratinizing cancers.

Clinical studies with adjunctive surgery and irradiation therapy in the treatment of carcinoma of the cervix

The majority of patients with cancer of the cervix are treated adequately by irradiation alone, and surgery is not necessary. A role for operation develops in certain patients with Stage I‐II cancer of the cervix, who are prone to develop central recurrence if treated by irradiation alone. In these patients the primary lesion is massive. The vasculature to the center of these bulky or barrel‐shaped cancers is insufficient, and a population of the cancer cells, perhaps related to anoxia, is more resistant to irradiation. The postirradiation conservative hysterectomy was incorporated into the treatment plan for 212 selected patients and the number of local recurrences was reduced. Incomplete cure of the peripheral component of the disease is another mechanism of treatment failure. This may occur, even though the primary lesion is cured. Patients with cervical cancers greater than 5 cm diameter have a high incidence of node metastasis, regardless of clinical stage. In those patients with positive nodes, the standard portals for external irradiation were expanded to include nodes at higher levels. The site of metastases was established by pretreatment laparotomy and the irradiation portals were then extended to include the involved nodes. Survival rates were not improved, because recurrences were not prevented, and death from treatment complications were high.

Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix: preliminary results of a randomized trial.

From September 1968 to March 1974, a randomized clinical trial was carried out, using conventional fractionation, i.e., five treatments per week, in 233 patients with advanced cancers of the uterine cervix—Stages IIB, IIIA IIIB and IVA. The age limit was 70 years and all patients had medical clearance. Lymphangiography and, in some patients, an exploratory laparotomy with selective lymphadenectomy, were done prior to treatment to determine the extent of nodal disease. The staging has not been changed either by lymphangiogram or lymphadenectomy findings. A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and/or lymphadenectomy. First, the patients were grouped according to the clinical stage. The second stratification was according to the lymphangiogram and/or selective lymphadenectomy findings. The patients were then randomized to air or hyperbaric oxygen within each group. The patients were pressurized in a Vickers chamber at 3 atmosphere absolute, using a 20‐minute soak time prior to the irradiation. The size of the external beam portal was determined by the status of the nodes. The difference in absolute NED (no evidence of disease) survival rates for both groups as a whole and by stages is not statistically significant. There is no difference in the incidence of failures in the irradiated area between the HPO and air patients. There is no increase in distant metastases in the HPO group. It does not seem that the HPO has had an effect on the major complications. However, there was an increase in the incidence of complications with extended fields. The addition of lymphadenectomy has increased the incidence of fatal complications, even with routine pelvic portals. The negative results of this trial with conventional fractionation should not lead to the conclusion that HPO could not be useful with schemes using few high dose fractions.

Guidelines for conservative hysterectomy after irradiation.

Abstract From September 1, 1954, through December 31, 1969, 155 patients with barrel-shaped endocervical carcinoma were treated with radiation followed by conservative extrafascial hysterectomy 6 weeks later. Thirteen patients developed fistulas involving the vagina and 5 patients developed bowel obstruction with an overall complication rate of a 11.6%. From January 1, 1970 through October 31, 1976, 102 patients were treated in a similar fashion. Only 4 patients developed severe complications. A critical review of the treatment features of the 15 patients who developed vaginal fistulas in both series identified pelvic inflammatory disease, blunt dissection, and excessive vaginal apex doses as contributing factors. The prerequisites for successful therapy without significant complications are absence of pelvic inflammatory changes before initiation of therapy, a conservative external radiation dose with cautious application and loading of the intracavitary system, meticulous surgical technique utilizing sharp dissection, and precautionary measures to avoid infection in the irradiated-operated pelvis during recuperation. Conservative extrafascial hysterectomy is adequate to encompass the disease if the patient has a true expanding endocervical barrel-shaped lesion, providing good protection against central failure.

Hexamethylmelamine: An evaluation of its role in the treatment of ovarian cancer

Hexamethylmelamine (HMM), NSC 13875, a synthetic agent structurally related to triethylenemelamine, has clinical antitumor activity and a role in the treatment of ovarian cancers of epithelial origin. Fifty-four patients, with International Federation of Gynecology and Obstetrics Stage III or IV carcinomas, previously untreated with chemotherapy or irradiation therapy, were treated with HMM (8 mg/kg/day) as a single agent at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, between January, 1973, and May, 1976. The response end points analyzed were complete plus partial response rate, duration of remission, and survival time. The complete and partial responses were verified whenever possible by second-look operation. Seventeen patients (31.8%) responded to HMM and three had no evidence of cancer, determined by multiple biopsies at second-look operation. Gastrointestinal, hematologic, and nervous system toxic effects were severe in 10 patients, requiring discontinuation of HMM. This study shows that HMM can induce a complete response and provide an extended disease-free interval without maintenance chemotherapy.

Whole pelvis megavoltage irradiation with single doses of 1000 rad to palliate advanced gynecologic cancers.

Abstract This study reviews the experiences at M. D. Anderson Hospital of treating advanced gynecologic malignancies for palliation with single doses of 1000 rad per fraction. When feasible, this treatment was repeated twice (for a total of 3 treatments between intervals of 3–4 weeks. The patients who received 3 treatments had the best palliation; 2 treatments were more effective than 1. The palliative response was good in cervix, vagina and vulva, poor in endometrial and ovarian carcinoma. The follow-up was short in some cases, but the acute complications appear minimal.

Results of treatment of early stage I carcinoma of the uterine cervix with intracavitary radium alone.

A total of 151 patients with Stage I carcinoma of the uterine cervix received treatment with intracavitary irradiation alone between 1948 and 1971. All patients had a minimum follow‐up of five years. There were no local failures. No patient with microinvasive carcinoma (Stage IA) had a regional failure. A maximum of 4% (4/93) of patients with invasive cancer less than 1 cm in diameter (Stage IB‐Small Volume) had regional failures. The five year determinate survival rates for patients with Stage IA and IB (Small Volume) lesions were 100% and 96% respectively. The incidence of severe complications was low, with a fistula developing in only one patient. Treatment with intracavitary radium alone is sufficient for patients with invasive cancer less than 1 cm in diameter who have adequate anatomy that allows effective irradiation of the primary lesion and paracervical lymphatics.

Preliminary report of the M. D. Anderson hospital randomized trial of neutron and photon irradiation for locally advanced carcinoma of the uterine cervix

Abstract Between February 1977 and August 1979, 75 patients with locally advanced carcinoma of the uterine cervix were randomized to receive treatment with: (a) a combination of 50-MeV neutrons and 25-MeV photons ± intracavitary radium (mixed beam group) or (b) 25-MeV photons ± intracavitary radium (photon group). The analysis of the total population revealed no difference between the mixed beam and photon groups with regard to local tumor control, frequency of major complications, or patient survival. There was a significant difference between the two groups with regard to the number of patients completing treatment with intracavitary radium. When the patients who completed treatment with intracavitary radium or an external beam boost are analyzed separately, the results with mixed beam irradiation are slightly better than those achieved with photon irradiation, although the difference is not statistically significant.