Holly H. Gallion

Transition from benign to malignant epithelium in mucinous and serous ovarian cystadenocarcinoma

The slides of all patients with ovarian cystadenocarcinoma treated at the University of Kentucky Medical Center from 1966-1990 were reviewed. Fifty-four serous tumors and 42 mucinous neoplasms were identified for further study. Benign epithelium adjacent to an area of borderline or malignant epithelium was observed in 74 tumors (79%) and a site of epithelial transition was noted in 38 cases (40%). The presence of associated benign epithelium was more common in borderline or well-differentiated lesions and in patients with early-stage disease. These findings are consistent with epidemiologic and molecular genetic data and suggest that certain benign serous or mucinous ovarian tumors have the potential for malignant transformation. Removal of these tumors, particularly in postmenopausal women, should result in a subsequent reduction in the frequency of ovarian cancer.

Conventional 3D conformal versus intensity-modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: a comparative dosimetric study of dose–volume histograms☆

OBJECTIVE The goals of this study were to evaluate the feasibility of pelvic intensity-modulated radiotherapy (IMRT) in the adjuvant treatment of gynecologic malignancies and to compare the dose-volume histograms (DVHs) and determine the potential impact on acute and long-term toxicity based on the dose to target and nontarget tissues for both planning techniques. METHODS Ten consecutive patients referred for adjuvant radiotherapy for gynecologic malignancies at the University of Pittsburgh School of Medicine and Magee-Womens Hospital were selected for CT-based treatment planning using the ADAC 3D version 4.2g and the NOMOS Corvus IMRT version 4.0. Normal tissues and critical structures were contoured on axial CT slices by both systems in conjunction with a gynecologic radiologist. These regions included internal, external, and common iliac nodal groups, rectum, upper 4 cm of vagina, bladder, and small bowel. Conventional treatment planning included 3D four-field box using 18-MV photons designed to treat a volume from the L(5)/S(1) border superiorly to the bottom of the ischial tuberosity on the AP/PA field and shaped blocks on the lateral fields to minimize the dose to the rectum and small bowel. A seven-field technique using 6-MV photons was used for IMRT. Restraints on small bowel for IMRT were set at 23.0 Gy +/- 5% and 35.0 Gy+/- 5% for the rectum and 37.5 Gy +/- 5% for the bladder while simultaneously delivering full dose (45.0 Gy) to the intrapelvic nodal groups in 1.8-Gy daily fractions. The dose-volume histograms where then compared for both treatment delivery systems. RESULTS The volume of each organ of interest (small bowel, bladder, and rectum) receiving doses in excess of 30 Gy was compared in the 3D and IMRT treatment plans. The mean volume of small bowel receiving doses in excess of 30 Gy was reduced by 52% with IMRT compared with 3D. A similar advantage was noted for the rectum (66% reduction) and the bladder (36% reduction). The nodal regions at risk and the upper vagina all received the prescribed dose of 45.0 Gy. CONCLUSIONS Intensity-modulated radiotherapy appears to offer several advantages over conventional 3D radiotherapy (3D CRT) planning for adjuvant radiotherapy for gynecologic malignancies. These include a significant reduction in treatment volume for bladder, rectum, and small bowel. It is anticipated that this reduction in volume of normal tissue irradiated would translate into overall reduction in acute and potentially late treatment-related toxicity. Prospective trials are necessary to better evaluate the advantages in a larger group of patients.

Transvaginal sonography as a screening method for ovarian cancer a report of the first 1000 cases screened

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirtyone patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one; serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA‐125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well‐accepted by patients. Currently, there are more than 3000 patient years of follow‐up in the screened population, and there have been no deaths due to ovarian cancer. A multi‐institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph‐vascular space invasion by tumor cells. Lymph‐vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph‐vascular space invasion as opposed to only 2% of patients without this finding (p < 0.001). Of seven patients with lymph‐vascular space invasion who experienced tumor recurrence, five developed extra‐pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph‐vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph‐vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

Small cell carcinoma of the uterine cervix

From 1962 to 1985, 2201 patients with invasive cervical cancer were staged, evaluated, and treated at the University of Kentucky Medical Center. After a thorough evaluation, 25 cases (1.1%) fulfilled the histologic criteria for small cell cancer defined by Reagan and coworkers. These patients were computermatched for age, disease stage, and lesion size to 25 patients with large cell nonkeratinizing cancer and 25 patients with keratinizing squamous cell cancer. Morphometric analyses of nuclear size and maximum nuclear diameter were performed on all cases without knowledge of cell type. Small cell cancers were characterized by a nuclear area of 160 μ2 or less and a maximum nuclear diameter of 16.2 μ, which was significantly lower than that for large cell tumors. Thirty‐three percent of the small cell carcinomas stained positively for the neuroendocrine markers (neuron‐specific enolase [NSE] and chromogranin [CGR]), whereas the remainder contained only epithelial markers such as cytokeratin (CYK) and epithelial membrane antigen (EMA). Small cell cancers were associated with a high frequency of lymph‐vascular space invasion and a diminished lymphoplasmacytic response. Patients with small cell cancer had a significantly higher recurrence rate, particularly to extrapelvic sites, than the matched patients with large cell cancers, and their survival was lower. Clinical trials to determine the efficacy of adjuvant chemotherapy in the treatment of small cell cervical cancer are needed.

Endometrioid carcinoma of the ovary and endometriosis: The association in postmenopausal women☆

Histologic material from 42 patients with endometrioid carcinomas of the ovary was reviewed. Ovarian endometriosis was present in 11 cases (26%) and 8 of these patients were postmenopausal. The exact site of transition from benign to malignant epithelium was observed in 4 cases. The clinical characteristics of patients with associated endometriosis were not significantly different from those without this finding except that endometriosis was present only in patients with Grade 1 or Grade 2 carcinomas. These data suggest that ovarian endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, should be removed surgically.

Randomized Phase III Trial of Standard Timed Doxorubicin Plus Cisplatin Versus Circadian Timed Doxorubicin Plus Cisplatin in Stage III and IV or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study

PURPOSE To determine if circadian timed (CT) chemotherapy results in improved response, progression-free survival (PFS), overall survival (OS), and lower toxicity, when compared with standard timed (ST) chemotherapy. MATERIALS AND METHODS Eligibility criteria were stage III, IV, or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery; measurable disease; and no prior chemotherapy. Therapy was randomized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2, or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm. Cycles were repeated every 3 weeks to a maximum of eight cycles. RESULTS The ST arm included 169 patients, and the CT arm included 173 patients. The objective response rate (complete responses plus partial responses) was 46% in the ST group compared with 49% in the CT group (P =.26, one tail). Median PFS and OS were 6.5 and 11.2 months, respectively, in the ST group; and 5.9 and 13.2 months, respectively, in the CT group (PFS: P =.31; OS: P =.21, one tail). Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group, versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group. Grade 3 or 4 leukopenia occurred in 73% of patients in the ST arm and in 63% of patients in the CT arm. There were eight treatment-related deaths. CONCLUSION In this trial, no significant benefit in terms of response rate, PFS or OS, or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma.

Combined radiation therapy and extrafascial hysterectomy in the treatment of stage IB barrel‐shaped cervical cancer

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 extrafascial 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 < 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 extrafascial hysterectomy. The findings of this study suggest that the use of extrafascial 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.

Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study.

Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment.