Richard E. Hunter

Initial clinical trials of the subrenal capsule assay as a predictor of tumor response to chemotherapy

Retrospective and prospective clinical trials were performed to determine the usefulness of the 6‐day subrenal capsule (SRC) assay for the prediction of response to chemotherapy. Evaluable assays were obtained in 86% of 1000 consecutive specimens obtained from a variety of solid malignancies. Analysis of chemotherapeutic sensitivity in this assay gave reproducible and consistent results. The overall predictive accuracy of the assay in 62 retrospective clinical trials in 55 patients was 85%. Of 37 evaluable patients with chemotherapy refractory cancers treated in a prospective trial with single agent chemotherapy as determined by the assay, 14 (38%) responded. Greater degrees of tumor regression in the assay were associated with a higher probability of clinical response. The SRC assay shows potential value as a rapid predictive test for chemotherapeutic selection on an individual patient basis. However, additional prospective clinical trials are necessary to document its ultimate utility. Cancer 52:2185‐2192, 1983.

Accuracy of frozen-section diagnosis at surgery in clinical stage I and II endometrial carcinoma.

OBJECTIVES: The purpose of our study was to determine if frozen section accurately identifies certain poor prognostic pathologic factors in endometrial carcinoma that are known to be associated with pelvic and paraaortic nodal metastasis, including deep myometrial invasion, poorly differentiated tumor, cervical invasion, adnexal involvement, and poor histologic type. STUDY DESIGN: The frozen-section pathologic results of 199 patients with clinical stage I and II endometrial cancer were retrospectively compared with permanent-section pathologic findings. RESULTS: The depth of myometrial invasion (superficial third vs deep two thirds) was accurately determined by frozen-section diagnosis at surgery in 181 of 199 cases (91.0%). The sensitivity of frozen-section diagnosis for deep myometrial invasion was 82.7%, and the specificity was 89.1%. The following tumor characteristics were accurately determined on frozen section at surgery: poorly differentiated tumor (95.0%), cervical invasion (94.0%), adnexal involvement (98.5%), and histologic type (94.0%). Frozen section underestimated deep myometrial invasion in 17.3% of patients with this characteristic and poorly differentiated tumor in 26.3% when compared with permanent-section diagnosis. In patients with unfavorable histologic types, papillary serous and adenosquamous carcinomas were the most commonly misdiagnosed histologic types by frozen section at surgery (70.6%). However, when the preoperative curettage pathologic findings were included, these inaccuracies in tumor grade and histologic type dropped to 15.8% and 35.3%, respectively. Only 13 of 199 patients (6.5%) were not correctly identified by frozen section at surgery as having poor prognostic pathologic features. CONCLUSION: Frozen section diagnosis at surgery is an important procedure that enables the surgeon to identify patients at high risk for pelvic and paraaortic nodal metastasis.

Serum squamous cell carcinoma antigen levels in invasive cervical cancer: prediction of response and recurrence

OBJECTIVE The rate of normalization of human chorionic gonadotropin or CA 125 in other gynecologic malignancies is highly predictive of response to therapy and recurrence. Serum squamous cell carcinoma antigen (SCC antigen) levels were studied in patients with invasive cervical carcinoma to determine if the rate of normalization was associated with outcome. STUDY DESIGN One hundred eighty-four patients were studied. A logistic regression of elevated SCC antigen levels was performed. RESULTS In primary squamous cell carcinoma the SCC antigen level was elevated in stages I, II, III, and IV disease and all stages combined in 24%, 57%, 67%, 71%, and 43% of cases, respectively. Only 27% of patients with nonsquamous carcinoma of the cervix had elevated SCC antigen levels. SCC antigen levels were elevated in 50% of patients with recurrent disease. In both primary and recurrent disease elevated SCC antigen levels decreased with effective therapy. Normalization of elevated SCC levels was associated with a complete response; however, logistic regression of SCC antigen values was not. CONCLUSION When initially elevated, SCC antigen assays aided in determination of response and detection of recurrences.

Primary radiation therapy for endometrial carcinoma: A case controlled study

PURPOSE Primary radiation therapy is generally considered inferior to a surgical approach for patients with endometrial carcinoma and is reserved for patients with a high operative risk. These patients are usually elderly, have multiple medical problems and frequently die of intercurrent disease. To evaluate the efficacy of primary radiation therapy a case controlled analysis comparing corrected survival of patients treated with primary radiation to patients treated with surgical therapy with or without radiation therapy was performed. METHODS AND MATERIALS Sixty-four patients treated with primary radiation therapy were retrospectively studied. A Kaplan-Meier product limit survival analysis was used to estimate survival among patients treated with primary radiation therapy. A case control study matched by clinical stage, tumor grade, and time of diagnosis was performed. The Mantel-Cox statistic was used to evaluated the equality of the survival curves. RESULTS Primary radiation therapy was used to treat 9.0% of the patients with endometrial carcinoma during the study period. Cardiovascular disease, diabetes, age greater than 80 and morbid obesity were the most common indications. Ninety percent of patients had either Stage I or II disease. Forty-eight of the 64 patients (75%) completed treatment which included both teletherapy and brachytherapy. Ten patients received brachytherapy only. Twelve complications, both acute and chronic, occurred in eleven patients (17%). Intercurrent disease accounted for 13 of the 36 (36%) of the deaths. Clinical stage of disease and histologic grade of the tumor were significant predictors of survival, p = 0.0001 and p = 0.013, respectively. The case controlled study of Stage I and II patients treated by primary radiation therapy matched to surgically treated controls showed no statistical difference in survival. Dilatation and curettage after the completion of radiation therapy was predictive of local control, p = 0.003. CONCLUSION Although surgery followed by tailored radiation therapy has become widely accepted therapy for Stage I and II endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

Steroid hormone receptors in adenocarcinoma of the endometrium

Abstract Estradiol cytosolic receptor levels were determined in tumor tissue of 73 patients with adenocarcinoma of the uterus. In 71% of the tumors, the estradiol receptor was >3 fmole/mg cytosol protein. An assay of 3 or more fmole/mg cytosol protein placed the tumor in the category of estrogen or progesterone positive. The levels of estrogen receptors were not related to the stage or histological grade of the tumor nor to the age of the patient. Progesterone cytosolic receptor levels were determined in 31 tumors. In 52% of the tumors the levels of progesterone receptor were >3 fmole/mg cytosol protein. No relationship could be demonstrated between the levels of progesterone receptor and the stage of the disease, the histological grade of the tumor, nor the age of the patient. Thirty-one cases were studied for the presence of both steroid hormone receptors and 52% of these tumors could be classified as both estrogen and progesterone receptor positive. Preoperative radiation appeared to interfere with the determination of the tumors receptor status.

Lymphoepithelioma of the uterine cervix

A patient with a squamous cell carcinoma of the cervix with marked lymphocytic infiltration is reported and the literature reviewed. Although the entity has been rarely reported in the United States, the Japanese literature suggests that patients with this variant may have a more favorable prognosis.