Biomedical subjects
Publications and source records attributed to R A Potish.
From 1953 to 1975, 330 children received megavoltage for benign or malignant tumors. Fourteen subsequently developed second neoplasms. The 30-year cumulative incidence of second neoplasms was 9.6%. The incidence of second malignant neoplasms may be lower following megavoltage radiation than following orthovoltage radiation.
From 1978 to 1983, 112 women with advanced cervical carcinomas received radiotherapy after pretreatment surgical staging. Five-year actuarial relapse-free survival rates were a strong function of lymphatic spread: 40% with periaortic node metastases, 50% with pelvic node metastases, and 84% without node metastases. Primary treatment failure had a distant component in 75% of recurrences (50% of recurrences with negative nodes and 85% of recurrences with positive nodes). It was concluded that adjuvant systemic therapy is necessary to substantially raise the probability of cure.
From 1973 through 1983, 27 women received postoperative open-field external beam abdominal radiotherapy as primary treatment of endometrial carcinoma. The 5-year survival rate was 71%. Two distinct prognostic groups were demonstrated. Patients with spread to the adnexa, peritoneal fluid, or both, had a 5-year relapse-free rate of 90%. Patients with macroscopic spread of cancer beyond the adnexa had a 5-year relapse-free rate of 0%. Guidelines are suggested for the radiotherapeutic management of endometrial cancer metastatic to the peritoneal cavity.
From 1953 to 1975, 341 children received megavoltage radiation and survived at least 5 years. Chemotherapy was administered to 189 of these children. Although the expected age-adjusted 30-year survival was 97%, the observed survival was only 83%. Late recurrence of primary tumor was responsible for 24 of 37 deaths. Other causes of death included second neoplasm (4 patients), infection (4 patients), central nervous system complication (2 patients), inanition (1 patient), motor vehicle accident (1 patient), and miscellaneous (1 patient). Thus, 36 of the 37 late deaths were secondary to either the original cancer, a new cancer, or the effects of treatments. Brain tumors and Ewing's sarcoma have more late deaths while neuroblastomas have fewer late deaths than expected. Even after 25 years of follow-up, the survival of this cohort does not parallel that of the general population.
From 1973 through 1982, 48 women received 4500 to 5075 rads to the paraaortic lymph nodes as part of their primary management for cancer of the uterine corpus. One patient developed severe enteric morbidity. Five-year survival rates were 52% in the total group, 57% in clinically staged patients, and 47% in surgically staged patients. Patients with surgically confirmed pelvic lymphatic spread had a five-year survival rate of 67%. Patients with surgically confirmed paraaortic spread alone or pelvic and paraaortic spread had five-year survival rates of 47 and 43%, respectively. Eighty-eight percent of recurrences were outside of the radiation portals. In contradistinction to much of the last decade's literature, radiation therapy has salvaged a substantial fraction of patients with nodal metastases, and morbidity rates have been acceptable.
A guinea pig model was used to evaluate luminal content as a factor in the development of acute radiation enteritis. Surgical bypass of one half of the small bowel created an isolated segment free of luminal contents. Radiation effects on this empty intestine were compared with effects on bowel in continuity, on intestine containing bile only, and on intestine containing pancreatic enzymes plus food. The animals were subjected to a single dose of 1600 rad via an abdominal port and killed 4 days later. Surviving crypts per circumference provided one index of the severity of the injury. Intestinal damage was further evaluated by histologic grading. Surviving crypts were significantly fewer for irradiated segments of bowel containing any of the components of the intestinal stream compared to either nonirradiated controls or irradiated but empty bowel. Histologic scoring revealed a gradation of injury, with progressively more severe damage in empty irradiated bowel, and in intestine containing only pancreatic secretion, bile, and all components of the luminal stream. We conclude that both bile and pancreatic secretions in the lumen enhance acute radiation-induced small-bowel injury.
Decision theory analysis is a systematic approach to decision making under conditions of uncertainty. Using formal decision analysis, we analyzed the clinical course of 275 patients with advanced cervical cancer. As selection in the application of surgical staging made survival comparisons difficult, enteric morbidity was used as a valued outcome. While the probability of severe enteric morbidity in patients who undergo extended field radiotherapy and surgical staging is twice as high as that in those not receiving extended portals and undergoing surgical staging (0.095 versus 0.050), the increased precision of defining those patients in need of extended portals resulted in very little increased morbidity in the total group. The difference in probability of enteric morbidity in patients with surgical staging and those without was 0.065 versus 0.061. Efforts to increase the proportion of patients with metastatic disease in the surgical staging group by using as stratifying parameters undifferentiated histology or possibly, in premenopausal patients, progesterone receptor levels may allow for the best survival therapeutic ratio as the maximum survival benefit will be gained by a minimum of enteric morbidity.
All patients with carcinoma of the cervix, FIGO Stage IB, treated at the University of Minnesota Hospitals during a 10-year period were reviewed. Of the 220 patients 31 (14.0%) developed recurrent disease and did not survive. Thirteen patients had pelvic wall recurrences, with concurrent cervical involvement. No patient had a resectable pelvic recurrence. Hysterectomy was subsequently performed on 10 of the 172 patients who received radiation therapy. Carcinoma was not present in any of the operative specimens although two patients with adenocarcinoma later died of metastatic cancer. Median time of recurrence was 9 months, with median survival following recurrence of 6 months. Cervical cytology was not of value in the early diagnosis of recurrent disease. The 5-year adjusted actuarial survival rate for patients with adenosquamous carcinoma was significantly lower than that for patients with squamous cell carcinoma. The median age of patients not surviving with adenosquamous carcinoma was significantly lower than that for patients not surviving with squamous cell carcinoma. Patients with invasive carcinoma presumably confined to the cervix may have disseminated disease. It is essential such selected patients receive primary treatment that includes systemic therapy.
From 1971 through 1981, 83 nonsurgically staged women with cervical cancer received extended-field radiotherapy on the basis of abnormal lymphangiogram, obstruction on intravenous pyelogram, or extensive pelvic tumor volume. From 1978 through 1981, 61 surgically staged patients underwent radiation therapy; of these, the 21 with positive lymph nodes received periaortic radiation. No increase in morbidity was found in these patients. Survival, relapse rate, and sites of treatment failures were similar in the positive lymphangiogram group and in the surgically staged patients with positive nodes.
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Sixty-one patients with invasive carcinoma of the cervix uteri underwent extraperitoneal pelvic and para-aortic lymph node sampling along with the exploratory laparotomy. Using the adverse surgical effects criteria modified from the G.O.G., the clinical course of this group of patients was analyzed, retrospectively. The demonstration of metastases had an adverse effect upon survival whether the metastatic disease occurred in the para-aortic or pelvic node regions. No substantial delay in the initiation of radiotherapy occurred regardless of the severity of toxicity.
To identify patients at high risk for the development of enteric injury, an analysis was made of 212 women who received extensive pelvic and abdominal radiotherapy at the University of Minnesota from 1970 through 1981. One hundred one patients with cervical carcinomas received 8,000 to 8,500 rads to point A, 6,000 rads to point B, and 4,500 to 5,075 rads to the periaortic lymph nodes. One hundred eleven women with ovarian cancers received 2,000 rads to the entire abdomen, followed by an additional 2,975 to 3,000 rads to the pelvis. The overall complication rate was 6.6% (14/212). The only patients who sustained chronic radiation morbidity had thin physiques. The maximum likelihood multiple logistic model was utilized to predict the probability of enteric injury as a function of thin physique, previous operations, and hypertension for individual patients. The usefulness of predictive models is discussed, and possible reasons for the susceptibility of thin women to ionizing radiation are explored.
From 1977 to 1981, 39 cases of primary cervical carcinoma were assayed for the presence or absence of cytoplasmic estrogen (ERc) and progesterone (PRc) receptors by a saturation point dextran-coated charcoal assay. The levels of ERc and PRc were compared with clinical stage, histologic type, histologic grade, menstrual status, age, and survival. Carcinomas were divided into positive and negative receptor groups with the use of greater than 5 fmol/mg of cytosol protein for ERc and 10 fmol/mg of cytosol protein for PRc as discrimination points. Survival of the patients studied was computed by means of the product-limit analysis according to Kaplan-Meier. A statistically significant difference in survival in the PRc + group versus the PRc - group in the total group of patients was noted with the Mantel-Cox test (P = 0.049). When patients were stratified according to menopausal status, a statistically significant difference in survival was noted between the PRc + group versus the PRc - group in the premenopausal patients only.
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The importance of risk factors in the development of radiation-related enteric damage has been demonstrated. Ninety-two women with ovarian tumors received 2000 rads to the abdomen, followed by an additional 2975 rads to the pelvis. By analyzing the development of small bowel obstruction in these women and in other series from the literature, it appears that more than half of enteric complications can be attributed to factors such as prior surgery, thin physique, and preexisting vascular damage. These constitutional factors often will have a greater effect on the development of small bowel damage than will radiation dose, volume, or time. By taking such factors into account and by substituting alternative forms of therapy when feasible, morbidity secondary to radiotherapy can be substantially reduced.
The relationships between the Fletcher and Manchester methods in dosimetry of cancer of the uterine cervix were explored in order to compare dose prescriptions between the systems, to optimize the best features of both systems, and to establish the necessity for computerized dosimetry. A total of 91 Fletcher-Suit radium applications was analyzed by a linear least-square regression analysis to compare Point A and Point B doses of the Manchester system will milligram-hours of the fletcher system. Although moderately high correlations were found between milligram-hours of radium and doses at Point A and Point B, it was concluded that direct comparisons, particularly between individual patients, are fraught with dose uncertainties of clinical significance. In addition, the correlation between milligram-hours of radium and Point A dose was markedly affected by the position of the colpostats and tandem, thus making it difficult to formulate a simple conversion factor between the two systems.
In order to predict radiation-related enteric damage, 92 women were studied who had received identical radiation doses for cancer of the ovary from 1970 through 1977. A logistic model was used to predict the probability of complication as a function of number of laparotomies, hypertension, and thin physique. The utility and limitations of such probability models are presented.